Psych 111: Lecture 12-17

Activity-dependent plasticity

Activity-dependent plasticity is known for its role in the pruning of synapses during development. The rules: "fire together will wire tother" and those "out of sync will lose the link" is based on the trafficking of AMPA receptors in the striate cortex based on LGN input. -Weak NMDA receptor activation by poorly correlated activity (from a closed eye) triggers loss of AMPA receptors. -Strong NMDA receptor activation by well-correlated activity (from open eye) maintains AMPA receptors.

Autonomic Nervous system(s)

Acts like diffuse modulatory system for entire body

Energy sources and feeding

Energy in the body is regulated homeostatically (sort of)... Low energy increases feeding and high energy decreases feeding. Body has several types of energy: -glucose is most readily useable energy (preferred by all cells; necessary for neurons) -glycogen is a short-term store of energy in liver and muscle -fat/lipid is a long-term store of energy in adipose tissue

Neuroadapatations to Repeated Drugs

Drug exposure produces homeostatic changes that tend to oppose the effect of the drug (i.e. adaptation opposes drug effects) resulting in tolerance. These same changes can be observed in the absence of the drug as withdrawal effects. Note: some effects of drugs increase with repeated exposure = "sensitization"

Sympathetic effects of stress response

Effects of epinephrine: -increased oxygen via a higher rate rate, respiration, etc. -increased glucose in blood via breakdown of glycogen in liver -does not cross blood-brain barrier --> more energy for muscle contraction

Paradigm for behavioral neurobiology of fear

Emotional memories appear distinct from explicit memories --> e.g. (conditioned) subconscious images.

Emotional expression

Emotions are associated with characteristic expression patterns (i.e. somatic muscle activation) which includes facial and body postures that convey social information to others. Evolutionary value?

What are emotions?

Emotions- subjective experiences arising from environmental stimuli. Emotions are largely characterized by subjective experience a.k.a. "feelings" which includes the cognitive label that we ascribe to the, Emotional experiences also have defined emotional expressive components; i.e. expressive components are overt observable patterns. Emotional experiences are associated with physiological correlates including hormonal, autonomic, and neural responses/states.

Early theories of Emotional Experience: James-Lange Theory

James-Lange Theory: sense/perceive --> expression --> experience " Not consistent with intuitive notion about emotions but what about experimental evidence to support that somatic responses influence emotional experience. But is there evidence for this?? i.e. does arousal impact emotional experience?

MORE memory in hippocampus

LTP in the hippocampus requires repeated co-activation of synapses (this is readily produced by prolonged high-frequency stimulation) because a single synapse is insufficient to induce LTP. This necessitates the detection of coincidence of synapse activation (by the NMDA receptor resulting in Ca++ influx). Those synapses firing together become linked (i.e. form "cell assembly" properties). This is referred to as co-operativity.

AND MORE

NMDA activation (and Ca++ efflux) is critical switch between LTP and LTD. i.e. determines induction. -also input specific, thus on a single postsynapitc neuron we can have weakening of a specific input (with eventual loss) and strengthening of other inputs.

Receptors for amino acid-derived and peptide hormones

-All are cell-surface proteins; these hormones do NOT enter target cells. -All have enzymatic activity [e.g. phosphorylate (kinases) or dephosphorylate (phosphatases) other proteins[. 1) receptors can be directly enzyme-coupled (e.g. tyrosine kinase). 2) Receptors can be G-protein-coupled to second messenger systems (e.g. cAMP). -Receptors often initiate transcription factors.

Memory in Hippocampus/Medial Temporal Lobe

-Although details are still unclear, evidence supports role for MTL for declarative memory, including hippocampus in some types of memory. Current models argue for different roles of different structures acting as a system/circuit (rather than localized function). -Synaptic plasticity remains highly supported in memory function (again details are still missing on how this works).

Motivation, emotion, and learning/memory cont.

-Although these psychological processes are distinct conceptually, they are mediated by overlapping neural circuits. -Accordingly, a single "system" may be underlying these different processes.

Control of Behaviors by Reinforcers

-Behavior is influenced by the presence of specific environmental stimuli that predict consequences: -Natural "rewards" (food, sex, etc), drugs, and electrical stimulation can control behaviors by acting as reinforcers (stimuli that alter the probability of behavior): 1) stimuli-response learning and response-consequence learning -Stimuli associated with rewards also control behavior. -Reinforcers and conditioned stimuli are often referred to as incentives because we will work for them.

Vascular (temperature) function and emotions

-Blood flow contributes to brain temperature and is activated by ANS (e.g. during stress). -Raising brain temperature biases emotional experience to anger. -Cooling brain temperature biases emotional experience to happiness. "hot-" versus "cool-headed" actually impacts emotional experience

Memory in Hippocampus: learning/memory and epigenetics

-CREB and related proteins are also part of the "epigenetic machinery" which can remodel chromatin producing long-term changes in gene expression. e.g. H3 acetylation will produce increased transcription for days-weeks. Acetylation can also lead to long-lasting changes in DNA methylation during learning. -Note: 5HT and DA (modulatory neurotransmitters) can impact changes induced by glutamate: diffuse modulatory systems can alter amount of learning via "convergence" within intracellular signaling cascades. -Missing pieces remaining include how epigenetics in nucleus matching up with changes in specific synapses.

Hormonal control of male sexual behavior

-Castration abolishes male sexual behavior in all species. -Testosterone restores male sexual behavior (however, temporal aspects are variable!!) -Individual differences in sex drive persist with equal testosterone levels. -Huge variation in human sex drive. -Human castrates can maintain sex drive (i.e. function of prior sexual experience). -Little correlation with testosterone levels except for hypogonadal men.

Hebbian Cell Assembly

-Cell assemblies involve many neurons (maybe 100-1000s( that are activated by an environmental event. -As the assembly continues to be active (reverberates), synaptic modifications are produced, with the level of activity (and modifications) being related to the importance of the event. -Reactivation of the assembly is produced by re-exposure to elements of the environmental events due to synapses strengthened by prior exposure induced neural activity (i.e. learning).

Cerebellum

-Cerebellum is highly convoluted with a huge surface area of functional units (i.e. functionally organized similar to cerebral cortex). In fact, it is like a third hemisphere of processing power. -Again, like the cortex, there is regional specialization in cerebellum including regions involved in learning (procedural memories).

Limbic: Lobe and Circuit

-Cingulate gyrus is a cortical lobe located at the border of the cerebral hemispheres (i.e. limbus described by Broca) and underneath other neocortical structures. -in the 1930s, Papez postulated that the unexplained neural bases of emotion was mediated by the uncharacterized cingulate gyrus. -consistent with neuropsychological evidence e.g. Phineas Gage -Papez expanded upon this idea and established the connections of the cingulate (gyrus) cortex: -concluded that the interconnected structures form a circuit which is known as the Papez circuit (Note: it is a subcortical processing loop similar to the "basal ganglia" of the motor system). -concluded that the circuit mediated emotional behavior.

Molecular aspects of BLA (basolateral amygdala) neuroplasticity in conditioned fear

-Critical roles of glutamate receptors. -Works the same as neuroplasticity in LTP in hippocampus: -NMDA is critical for acquisition of learning/inducing plasticity which results in -Changes in the number of AMPA which mediates long-term change in synaptic strength.

Hormonal control of female sexual behavior

-Cyclic changes in gonadal steroids (estrogen and progesterone) controlled by HPG. -Hormone levels interact with social settings to determine sexual behavior" -male controlled (paired) copulation not tightly linked to menstrual cycle. -female controlled (group) copulation tightly linked to menstrual cycle.

Chronic stress and hippocampus

-Dendritic morphology decreases in hippocampus after chronic stress. -Also have reduced cell number (due to reduced adult neurogenesis and increased cell death). -reduced overall hippocampus size.

H.M. patient continued

-Despite complete inability to form new long-term declarative memory, short-term/working memory and memory retrieval was normal. --> specific disruption of consolidation -non-declarative memory functions were also normal -implicit memory was normal e.g. exhibited "priming" effects -procedural memory was normal e.g. motor tests, puzzles

Lateral Hypothalamic Area

-Diverse projections throughout forebrain, including limbic system, motor system, cerebral cortex. -Inject NPY and AgRP --> stimulates feeding behavior -Inject alphaMSH and CART --> inhibit feeding behavior

Serotonin and Dopamine during sexual behavior

-Dopamine is elevated during copulation but falls after ejaculation --> excitement/saliency -Serotonin is elevated only following ejaculation (similar findings with opioids) --> satiety (reward?)

How drugs affect the brain

-Drugs act on neurons by altering neurotransmission at receptors, alter synthesis, release, etc. -Action in brain requires drug to pass blood-brain barrier and bind to proteins. -General idea of drug of abuse is that they usurp normal brain functions.

Metabolic phases of stress-response

-During the initial phase of the stress response, glucose levels rise due to glycogenolysis in the liver under regulation by epinephrine. -During HPA activation, cortisol (a glucocorticoid) maintains blood glucose levels by gluconeogenesis (conversion from amino and fatty acids) under control of cortisol to allow prolonged elevations.

Endocrine Glands of the body

-Endocrine glands are found throughout the body and are connected to the blood system. -Brain also has endocrine gland in the hypothalamus. -Endocrine glands are involved in coordinating cell activity in every part of the body by releasing hormones.

principles of homeostatic regulation

-Function of cells depends on tight control of extracellular environment ("internal milieu"), including water, nutrient, energy (sugar), and temperature levels. -Organism must compensate for disturbances in internal milieu. -Brain serves as control center for monitoring internal milieu. -Hormones serve as messengers between brain and body. -Regulation involves negative feedback control on behavior: -low water in body leads to increased thirst -low food energy leads to increased hunger -low temperature leads to increased thermogenesis

Hypothalamus and Pituitary

-Hypothalamus is located at the base of the brain and has direct connections to the pituitary via blood and neurons (axons). -Together the hypothalamus and pituitary serve to regulate many peripheral endocrine glands. -Paraventricular nucleus of the hypothalamus is considered the master gland of the endocrine system.

Limbic: System

-In the 1950s, MacLean revised Papez's work leading to a more encompassing group of structures in the forebrain cortex (telencephalon) and sub cortex (diencephalon) involved in emotion which he termed the "limbic system." -Although there is continuous debate over whether this constitutes a system equivalent to sensory or motor systems and which structures should be included. -But these structures do interact to mediate the psychological processes of motivation, emotion, and (several forms of) memory.

Time keeping in the SCN

-Individual cells in SCN are capable of generating circadian rhythms via mRNA-protein interactions. -Cells are coupled by gap junctions. Visual input allows synchronization with the environment. Chemical output to brain coordinates brain structures (including diffuse modulatory systems).

Simple Systems approach

-Invertebrates have simple (small number of neurons) nervous systems with huge neurons (easily identified; e.g. squid giant axon) that often operate much more independently than in mammalian systems. e.g. single neuron carries all sensory information between a structure and the central nervous system. -Invertebrates also show responsiveness to environmental stimuli (e.g. gill-withdrawl reflex) than can be modified (i.e. undergo learning processes).

Summary of steroid effects

-Membrane incorporation of steroid receptor and "classic" genomic effects -Modulation of channel-receptors -modulation of G-prtoein coupled receptors

What is motivation?

-Motivation is the reason or reasons for engaging in a particular behavior, especially human behavior as studied in psychology and neuroscience. The reasons may include basic needs such as food or a desired object, goal, state of being, or ideal. The motivation for a behavior may also be attributed to less-apparent reasons such as altruism or morality. -According to Geen, motivation refers to the initiation, direction, intensity, and persistence of (human) behavior.

Nucleus Accumbens and Lateral Hypothalamus

-NAc lesions in naive but not experienced male rats impairs both psychogenic erections and copulation (i.e. learning occurs during copulation). -LHA lesions in male rats facilitates erection (i.e. normally serves as an inhibitory role) but blocks ejaculation.

Connectivity of prefrontal cortex

-PFC has extensive connections with both the limbic structures and basal ganglia. -Decisions are intimately connected to learning, motivation, and emotions.

Subconscious emotions: expression without experience

-Perception of angry face can be masked by neutral face -Conditioned emotional expression are still manifest when perception is absent

NAC topography: appetite vs. aversive

-Research on taste reactivity (and other phenomenon) suggests that subregions of the NAC are relatively selective to hedonic (appetitive) vs. aversive stimuli with more anterior regions involved in hedonics and more posterior regions involved in aversion. (these effects can be modified by learned [conditioned] components of the environment). -Thus, good and bad are encoded at different levels of the limbic-motor system by anatomically distinct structures (i.e. analogous to topographically encoding of stimulus info in sensory systems).

SCN and sleep

-SCN provides gross temporal control of sleep patterns (i.e. sleep versus wake). -Neural circuits for inducing the sleeping "brain state" are in the brain stem: 1) ponts/pontine, raphe, locus coeruleus, reticular formation; i.e. the diffuse modulatory system(s)--NE, 5HT, Ach involved in coordinating brain activity. 2) These are complex systems that are also involved in arousal of brain during waking states as well as sleep (i.e. sleep is an example of how these systems work).

Regulation of steroid levels

-Steroid hormones are not stored. -Steroids are released as they are synthesized. -Levels of steroid are regulated by control (e.g. phosphorylation) of synthetic enzyme activity that convert cholesterol to active hormones. -Response to release signal is slow and prolonged.

Steroid receptors in membrane

-Steroid receptors can also be localized to the membrane allowing interactions with second messenger systems. 1) effects via membrane receptors are much faster than nuclear receptors. 2) Can be independent of protein synthesis. 3) These systems are poorly understood.

Dopamine and reinforcers continued

-The VTA neurons are activated under initial reward/incentive learning prediction and when there is an unexpected event (i.e. reward omission). -DA implicated in learning about rewards (but not neural mediation of the reward).

Nature of learning and memory

-The basic functional property of learning/memory is the utilization of information for a later time point. -This requires that information be not only encoded by sensory/perceptual systems but that the information is somehow stored (i.e. maintained within the brain) and retrieved at the later time point. -Major structures involved in learning/memory are largely known. -The physiological substrate of memory is referred to as the "engram" and the basis of this is just starting to be understood.

Procedural learning in cerebellum continued

-The involvement of the cerebellum in classical conditioning of the eye blink reflex has been widely described. -Various stimuli (UCS) produce eye blink reflex e.g. air puff. -Pairing neutral stimuli (CS) with an eye blink producing stimuli (UCS) will result in the initially neutral stimuli to acquire the ability to produce eye blink conditioned response (CR). -The plasticity of underlining this learning occurs int he cerebellum. -Specifically, there is long-term depression (weakening of synaptic strength) in specific synapses resulting in behavioral changes to environmental stimuli.

Common substrate in sex and feeding

-hormone-induced "drive" -mesolimbic dopamine -lateral hypothalamus serotonin from Raphe (also opioids) -PVN regulation of endocrine system -Cortex, limbic system, etc.: controls specific aspects of motivated behavior. But very different endocrine controls

Medial Preoptic Area (mPOA)

-mPOA lesions impair copulation and sexual arousal in males. -Binds sex steroids to mediate restoration. -Convergence site for sexual sensory pathways (somatosensory and olfactory). -A major activator of mPOA is phermonal stimulation via amygdala (i.e. limbic input). -mPOA also receives other sensory inputs e.g. somatosensory (genitals), visual? auditory? -mPOA is part of a larger circuit involved in sexual behavior. -Has descending outputs through brain stem (BS) to control arousal and orgasm (ejaculation). -Has outputs to VTA diffuse modulatory system.

Circadian rhythms are...

... coordinated by suprachiasmatic nucleus (SCN)

Actions of Hormonal Satiety Signals

1) Leptin and insulin circulate in the blood in concentrations proportional to body fat content and energy balance. 2) Leptin and insulin act on central effector pathways in the hypothalamus, repressing brain anabolic neural circuits that stimulate eating and inhibit energy expenditure, while simultaneously activating catabolic circuits that inhibit food intake and increase energy expenditure. 3) Low leptin and insulin levels in the brain during weight loss increase activity of anabolic neural pathways that stimulate eating and suppress energy expenditure, and decrease activity of catabolic pathways that cause anorexia and weight loss. 4) Ingestion of food generates neural and hormonal satiety signals to the hindbrain. Leptin/insulin-sensitive central effector pathways interact with hindbrain satiety circuits to regulate the meal size, thereby modulating food intake and energy balance.

conceptualized storage of information

= synaptic rearrangement. The notion that information stored by memory involves specific synaptic modification/rearrangement was posited by Donald Hebb. The proposed that neural activity was the key event in "wiring the brain. (based on developmental mechanisms). Essentially neurons that "fire together will wire together" and those "out of sync will lose the link".

Protocol for inducing conditioned fear

Acquisition and expression of learned response is dependent upon the amygdala. Key is to examine the emotional expression in response to conditioned stimuli i.e. able to elicit emotion

MORE

AMPA trafficking is a common mediator of increases (LTP) and decreases (LTD) in synaptic strength. i.e. determine expression of neural plasticity.

Adrenals and stress responses: HPA and sympathetic nervous system

Adrenal cortex (activated by HPA) and medulla (activated by ANS) tend to have synergistic effects on peripheral tissue. Adrenal gland contains the medulla and cortex.

Endocrine aspect of sympathetic NS.

Adrenal medulla acts as specialized "post-ganglionic" neuron to release epinephrine into circulation. -stimulated by Ach -activated synchronously with rest of sympathetic ANS. No parasympathetic innervation.

More and more and more memory in hippocampus

All long-term memory requires protein synthesis (inhibit synthesis will produce amnesia). A number of transcription factors appear to be involved, including the cyclic AMP response element binding protein (CREB). CaMKII (and other kinases) can phosphylate CREB which induces transcription.

Steroid hormones

All steroids are derived from cholesterol and are lipid soluble.

The amygdala

Amygdala is an integral part of the limbic circuitry: -extensive multimodal inputs from association cortex and hippocampus. -extensive outputs to prefrontal cortex, nucleus accumbens, and hippocampus. Distinct nuclei of the amygdala perform distinct processes in conditioned fear.

Stress response and performance

An inverted "U" response of stress (in form of glucocorticoids) and performance applies to many tasks, including sexual and immune function (under acute stress conditions). -A little bit of stress improves performance and high stress generally reduces performances.

Human emotions and amygdala

Angry or fearful faces activate amygdala. Happy faces activate amygdala in some studies but not others; may involve contextual factors. -Amygdala disp,ays highest activation when mixed emotions are present; -indicating amygdala is sensitive to both positive sand negative emotional expression.

Hypothalamic circuit regulating feeding

Arcuate nucleus detects satiety and feeding hormones and regulates behavior through other nuclei.

Arcuate Nucleus Neurons

Arcuate nucleus integrates information on blood glucose levels (insulin) and body fat levels (leptin). Two types of arcuate nucleus neurons are responsive to both insulin and leptin: -Neuropeptide Y (NPY) and Agouti-Related Peptide (AgRP) expressing neurons. -alpha-Melanocyte stimulating hormone (alphaMSH) and cocaine and amphetamine-regulated transcript (CART) expressing neurons. These neurons have opposing effects on feeding behavior and metabolism via interconnections with other hypothalamic structures.

More on the memory in hippocampus

As with other forms of synaptic plasticity, LTP is produced by modifying the function of AMPA receptors either by phosphorylation to increase function of individual receptors or by trafficking more receptors to membrane at synapse.

The Hedonic Homeostatic Hypothesis

Based on the idea that we have an optimal desired reward state, addiction can be described as a cycle of binging followed by withdrawal effects that include anhedonia (emotion dependence) resulting in preoccupation with drug-taking. There are neural mediators of different phases of addiction cycle: -bing: increase dopamine, opioids. -withdrawal: decrease dopamine, opioids, increase stress hormones

Amygdala and (conditioned) fear expression

Basolateral amygdala is believed to be site that mediates the association of US + CS and projects to cerebral cortex, nucleus accumbens, hippocampus. Central nucleus projects to brain stem and hypothalamus produces autonomic responses.

long-term regulation of energy: body weight

Body weight is generally stable around a "set point" but will change with long-term changes in feeding; primarily due to changes in adipose tissue. "Lipostatic" hypothesis - fat levels are key target (and have a set-point) in long-term regulation of energy: -adipose tissue serves as long-term energy storage. -adipocytes release hormone in proportion to size -amount of adipose tissue controls feeding -Adipose cells release leptin which inhibits feeding

Hypothalamus-pituitary-gonadal axis

Brain: neural signals --> Hypothalamus: releases gonadotropin-releasing hormone --> Anterior pituitary: releases gonadotropin --> gonads: release estrogens, androgens, and progestins --> body tissues Positive or negative feedback influences the subsequent release of hormones. Behavior is influenced by gonadal hormones acting on the brain.

Memory in Hippocampus again

Calcium-Calmodulin-dependent protein Kinase II (CaMKII) is critical for neural plasticity. -it can autophosphorylate to maintain the NMDA-mediated efflux of Ca++ for prolonged periods which allow long-term changes in cellular function (i.e. protein synthesis). -seves as a molecular switch for inducing long-term changes believed to underlie memory.

Early theories of emotional experience: Cannon-Bard theory

Cannon-Bard Theory: Sense/perceive --> experience --> expression: Consistent with: -intuitive notion about emotions and -evidence that thinking of emotional experiences induces emotional expression (e.g. increase adrenalin, heart rate, etc).

Early theories of emotional experience and expression

Cannon-Bard Theory: argues that the feelings of fear are evoked by a stimulus and produces a physiological expression. James-Lange theory: argues that physiological arousal are triggered by stimulus and feelings are the cognitive labels that we impose upon the arousal.

Protocol for inducing contextual conditioned fear

Contextual conditioned fear: Phase 1: context (distinct place) with foot-shock. Phase 2: present contextual cues in absence of foot-schock and measure emotional expression (freezing). Acquisition and expression of this learned response is dependent upon the amygdala and hippocampus.

procedural learning in cerebellum

Cerebellum is primarily involved in fine-tuning motor output; receives proprioceptive info and adjusts motor commands. Purkinje Cell (PC) is major output of cerebella, -PC receives glutamate (excitatory) input form climbing fiber axons from medulla carrying proprioceptive info. --> "what is going on" signal. -PC receives input from granule cells via parallel fibers. Granule cells receive input from mossy fibers which is a neocortex input via brain stem. --> "what we want going on" signal

Simple systems approach and again

Classical conditioning in a simple system: -Gill-withdrawl reflex is also capable of exhibiting associating learning: If non-effective stimulation of siphon (CS) is parroted with shock to tail (US) then CS will come to elicit a gill-withrdrawl reflex (CR).

Types of Hormones

Classification on source: i.e. gonadal, adrenal, thyroid, etc. Classification of messenger: 1. peptides 2. steroids

Memory in Medial Temporal Lobe

Cortical structures including those involved in declarative memory (e.g. DNMS) also exhibit long-term depression (LTD) and long-term potentiation (LTP) plasticity which is dependent on NMDA receptors for induction (and perhaps common molecular changes to plasticity in the hippocampus).

Walking and glucocorticoids

Cortisol shows a circadian rhythm that rises late during rest and peaks at the start of walking. -allows mobilization of energy when you need it. -Anticipates needs (e.g. compare versus temperature). -Also get increases in cortisol during copulation, exercise or after taking cocaine, alcohol, and other drugs of abuse; -glucocoricoids increase when you need a metabolic response whether it is for good things or bad things.

Theories of drug addiction: "negative" theories

Dependence Theories of Addiction: dependence can be physical and motivational/emotional -Main prediction is that addicts seek drug in order to avoid negative consequences of being drug-free. -For instance, take drug to avoid drug withdrawal syndrome associated with physical dependence. -Withdrawal symptoms can be conditioned, that is triggered by drug-paired cues, explains relapse after long-term abstinence.

Diffuse modulatory systems

Discrete nuclei send vast projections (releasing either Ach, DA, NE, or 5HT) throughout the brain serving to coordinate brain function... i.e. induce brain states (e.g. sleep versus wake; excited vs. relaxed etc.). Neurotransmission is reciprocal (indirectly; i.e. the nuclei which send diffuse projections are under control of other brain regions). e.g. glutamate projections form PFC to VTA/raphe, etc.

H.M.

Epileptic patient with foci in medial temporal lobe --> epilepsy cured by removal of foci. Appeared normal but exhibited declarative memory deficits. -retrograde memory was intact (memories before the accident) -anterograde memory was impaired (memories after the accident) --> short-term memory was intact but long term memory was lost. -could remember a person's name in conversation but had to be reintroduced later -could do the same crossword or watch same TV show over and over -if lost would return home but it was the one he had lived in prior to surgery

Sympathetic arousal influences emotions: the Capilano Bridge Experiment

Experiment: found that men walking across this bridge were much more likely to be attracted to the female interviewer than men walking on a much safer bridge upstream. Apparently it was difficult for men to distinguish between the emotions of fear and sexual arousal. Also, injections of adrenalin evoke feelings in the absence of obvious environmental stimuli. Stress responses (presumably due to autonomic afferents/feedback) can impact the emotional experience.

short-term control of feeding

Feeding reflects internal states of hunger and satiety. Meal consumption (i.e. food) triggers satiety signals (insulin, leptin, CCK, gastric distention) complete with hunger signals (ghrelin) to regulate feeding.

Hungry?

Food stimuli (sight, smell, sound, etc) have a major influence on motivation for food... why do you think they spend so much on advertising? Motivation for food is influenced by many factors, including drugs and hormonal states.

Metabolic effects of glucocorticoids

Generally, provides prolonged elevation of metabolic resources i.e. blood glucose for muscle and brain. This one effect is opposite that of epinephrine..

Memory in Hippocampus yay

Glutamate and Synaptic plasticity: -As in other forms of plasticity, Hippocampal LTP (and LTD) involves NMDAR (acquisition) and AMPAR (expression) receptor co-activation. Also, have metabotropic glutamate channels. These are slow but modulate the effects of NMDAR to induce and consolidate plasticity (i.e. prolong glutamate will produce larger effects).

ARC inhibition of feeding

HIgh insulin and leptin levels: alpha MSH/CART neurons of arcuate nucleus: stimulate release of ACTH and thyrotropin from anterior pituitary --> inhibit feeding behavior

Simple Systems approach continued

Habituation (non associative learning) in a Simple system: -repeated stimulation of siphon will induce a reduction in gill-withdrawal reflex -Reflex habituation occurs with a reduction in firing of motor (L7) with no firing change in sensory neuron (i.e. same transduction encoding). This is an example of modulation of synaptic strength/

declarative memory in medial-temporal lobe continued

Hippocampal complex plays an important role in declarative memory as measured by delayed non-matching to sample. -original studies in primates (1970-80's) with Medial Temporal Lobe lesions (i.e. several structures, including hippocampus) replicated H.M.-like "amnesia" -Rodent studies (1990's) failed to see these effects.. Peri-rhinal (PR) cortex is critical structure for MTL (medial temporal lobe) model of amnesia (i.e. deficit in DNMS (delayed non-matching to sample) produced by damage to only PR). Removal of just hippocampus induces no/very mild DNMS deficit. (so what does hippocampus do...)

Declarative memory in medial-temporal lobe

Hippocampus and related medial temporal lobe structures are critical for declarative memory (i.e. type of info loss in H.M>). -Hippocampus receives input form entorhinal cortex (highly multimodal) and has outputs through fornix to diencephalon (thalamus, hypothalamus, mammilary bodies, amygdala, striatum...)

Memory in hippocampus: Thinking spatially versus relationally

Hippocampus appears to be most closely linked to relational memory. That is remembering the linkage between multiple stimuli. e.g. where object are in space, contextual stimuli, occasion-setting stimuli

memory in hippocampus again

Hippocampus circuitry is well described and extensively examined for neuroplasticity. Entorhinal cortex has input to dentate gyrus. DG output goes to CA3. CA3 output forms fornix (major output of hippocampus to diencephalon) and also to CA1. Plasticity can be induced at many of these synapses but is most well characterized in the CA3 --> CA1 synapse

memory in hippocampus

Hippocampus is very involved in remembering places: -damage prevents and recalling places. -Activity associated with navigation and specific places. Also, roles in "emotional" regulation which may be distinct (functional and anatomically). Navigation in the hippocampus involves interactions with other MTL structures such as entorhinal cortex (e.g. hippocampus = place cells and ER = grid cells).

Thermostat model of homeostasis

Homeostatic system involves: -set point, -regulatory/monitoring system, and: sensor; control/effector systems. Homeostatically regulated behavior are believed to work in the same manner: decrease in "needed" object are detected resulting in activation of an "effector" system (may have many components) is activated to correct "balance."

Hormones vs. Neurotransmitters

Hormone = messenger molecule that travels in the blood. Hormones come from endocrine glands and brain.

Hypothalamus-Pituitary-Adrenal Axis

Hypothalamus - (CRH)-> anterior pituitary -(ACTH)-> adrenal cortex -(cortisol)-> blood Negative feedback in the HPA axis. Note: glucocorticoids: cortisol and corticosterone; species differences

Central control of ANS

Hypothalamus is a critical integrator of forebrain states (as well as bodily states via hormones; next) which regulates ANS activation. Sympathetic pre-ganglionic cell bodies are located in thoracic and lumbar spinal cord. Parasympathetic pre-ganglionic cells are located in posterior brain stem and sacral spinal cord.

The hypothalamus-anterior pituitary system

Hypothalamus produces "releasing hormones." Anterior pituitary produces "trophic hormones (hormones that have other endocrine glands as their target)." Peripheral gland have metabolic effects on tissue. Negative feedback to hypothalamus and anterior pituitary. Hypothalamus (brain) regulates peripheral endocrine glands; endocrine system feedback onto the hypothalamus. Hypothalamus -> "releasing hormones" Pituitary -> " trophic hormones"

Hypothalamus and anterior pituitary

Hypothalamus projects axons through the hypothalamo-pituitary portal system (vein) which carries hormones to the anterior pituitary. Anterior pituitary cells respond to hormones and release other hormones in general circulation; "endocrine relay".

Hypothalamus and posterior pituitary

Hypothalamus projects axons to the posterior pituitary. Axon terminals release hormones into blood. Release vasopressin (a.k.a. ADH) and oxytocin.

Vasopressin/ADH (anti-diuretic hormone) and water regulation

Hypothalamus-posterior pituitary interacts with peripheral tissues in regulation of hormones to regulate water retention (and thirst is regulated via central "limbic system"). Vasopressin = anti-diuretic hormone (ADH)

Theories of drug addiction: "positive" theories

Incentive theories of addiction: -Main prediction is that addicts seek drug in order to experience the positive effects of the drug. -For instance, seek drug to get "high"; euphoria, improve mood, etc. -Some evidence suggests that sensitization to the incentive value of the drug (i.e. addict want the drug more and more with repeated exposure) despite tolerance to drug's good/high-producing effects (i.e. addicts does not like drug effects).

LAST memory in hippocampus

Intracellular changes (e.g. increase AMPA signaling) are accompanied by increased extracellular changes that result in a "extracellular matrix" of protein which help to make the synapse larger and more enduring.

The stress response

Involves two components that coordinate autonomic system and endocrine system (under control of the brain). The fastest response to stress is the activation of the autonomic nervous system (ANS). ON in seconds. The slow response to stress is activation of the hypothalamus-pituitary-adrenal axis (HPA) ON in minute(s).

Lipid-soluble messengers (e.g. steroids)

Lipid soluble messengers (e.g. steroids) have special binding proteins and receptors.

memory in hippocampus-LTD

Long-term depression (LTD) is produced by low frequency tetanic stimulation of the CA3 fibers innervating the CA1. Again like other forms of neural plasticity, LTD is in put specific. LTD = depressed (weaker) synapse

more memory in hippocampus

Long-term potentiation (LTP) is produced by high frequency tetanic stimulation of the CA3 fibers innervating the CA1. Like other forms of neural plasticity, LTP is input specific. LTP = potentiated (stronger) synapse

Types of Learning and Memory

Many system(s) in the brain are used to acquire, store (consolidation), and retrieve information. There are multiple types of learning/memory (i.e. for different types of information) which seem to have somewhat independent neural substrates.

Contributions of the dopamine systems

Mesocorticolimbic system (from midbrain to VTA to PFC, cingulate, limbic, and nucleus accumbens) - mediates changes with motivation/goal-directed behavior. Mesostriatal system (from midbrain SN to dorsal striatum, basal ganglia) - mediates changes with habitual responding.

Recent theories of emotional experience

Modern theories of emotionality propose convergence of cognitive and somatic responses (expression) for perception of emotional experience. Involves parallel systems for experience and expression (with interaction between systems).

Motivation (simple version)

Motivation is the "driving force" for behavior which stems from two inter-related processes: 1) drive-reduction - reduce need 2) hedonic - increase pleasure Homeostatic versus non-homeostatic motivation.

Mesolimbic dopamine as a common substrate for abused drugs

Much of drug abuse and addiction can be explained by pharmacological effects on endogenous motivation systems (e.g. almost all drugs of abuse can increase mesolimbic dopamine). "drugs usurp endogenous incentive salience systems". A common action of stimulant drugs is to impact dopamine by altering uptake via transporters. These drugs also alter norepinephrine and serotonin (i.e. monamines involved in diffuse modulatory systems). Note: these also targeted by antidepressants. -Natural reinforcers (e.g. food and sex) increase extracellular dopamine in the nucleus accumbens. -Drugs of abuse are more potent than natural reinforcers/reward, and, thus can usurp normal brain functions. -This increased strength also appears to be associated with greater neuroplasticity/adaptations

Nucleus Accumbens (NAC): limbic-motor interface

NAC has multiple limbic inputs (with topographical organization). NAC has outputs to dorsal striatum through striatal-nigro-striatum "spirals". -NAC input to dorsal striatum is largely indirect via brain stem circuits.

Glutamate, post-synapitc density and scaffolding proteins

Networks of proteins coordinate channel-coupled and metabotropic receptors "postsynaptic density". -PSD-95 is critical for glutamate-induced plasticity.

Types of chemical communication

Neurotransmission-point to point; also have the local neurons; process parallel paths of information. Diffuse modulatory- coordination throughout the brain. Autonomic- parallel networks throughout body. Endocrine- blood stream throughout body to all cells.

types of learning and memory

Non-associative learning: -involves change in response to repeated exposures to stimulus -can decrease (habituate) or increase (sensitization) level of response. Associative Learning: -involves "relational" change in response to repeated exposure to stimuli -typically, involves predictive value of initially "neutral" stimuli in relation to meaningful stimuli -e.g. classical conditioning

Non-homeostatic Motivation

Not all behavior is directed to restore homeostasis or prevent homeostatic disturbances. e.g. sexual behavior These behaviors are motivated (i.e. involve endogenous "drives") and goal-directed and share some neural substrates as homeostatic motivation. BUT can not be explained in terms of homeostatic theories!

temporal aspects of memory continued

Nueropsychological and experimental evidence indicate that even for long-term memories there are temporal gradients. For instance, memory loss (amnesia) associated with trauma. Amnesia associated with a specific event (e.g. brain damage, seizures, excessive alcohol exposure etc.) and can be: -"retrograde" (before event); not this is not usually complete. -"anterograde" (after event) or -"global" (both).

PFC in memory

PFC has complex contribution to memory and is involved in several different forms of memory. -PFC involved in working memory = "info in mind"; -PFC appears to be critical for regulation of memory: an interesting example is that damage to the PFC often results in increased levels of "confabulation" (making stuff up; not quite lying) in which the afflicted person actually believes the made up story.

The Hypothalamus

Periventricular zone of hypothalamus: coordinates brain function with rest of body is critical for: -Circadian (sleep/wake) cycles -autonomic nervous system regulation -endocrine regulation

Prefrontal cortex and emotionality

Phineas Gage received damage to the PFC resulting in extensive changes in executive function (irrationality) and emotionality (rage). PFC is involved in both of the major processes (learning/memory and emotion) attributed to limbic system function. So should it be considered part of the system?

Serotonin and food reward

Serotonin in the lateral hypothalamus increases during both anticipatory and consummatory aspects of feeding behavior. Serotonin appears to be important for the hedonic or positive affect aspects (a.k.a. reward) of goal-directed behavior; Opioid peptides are also involves in similar function for feeding i.e. 5HT and opioids ~ reward.

Spinal Lesions and emotions

Spinal injury reduces the experience of emotion. The extent of the loss of emotionality is greatest when the lesion is high on the spine. Higher the lesion, the greater the reduction in emotion experience (i.e. blunted affect) which correlates to reduced peripheral autonomic (and somatic) input.

Procedural Learning in Striatum

Procedural learning is associated with plasticity in the dorsal striatum (part of basal ganglia). -treatment of NMDA with antagonists or disruption of dopamine system can block learning and related changes. Procedural and declarative learning/memory are completely dissociable: -amnesic vs. parkinson's disease patients.

Paraventricular Nucleus (PVN)

Projects to (i) anterior pituitary which regulates endocrine system and (ii) brainstem and spinal cord nuclei regulating autonomic nervous system. . -Inject NPY and AgRP --> decrease metabolic activity: -decrease thyroid stimulating hormone (TSH) and adenocorticopin releasing hormone (ACTH) -decrease sympathetic nervous system activity -Inject alphaMSH and CART --> increase metabolic activity: -increase TSH and ACTH -increase in sympathetic nervous system activity

Stress activates the HPA

Psychological "stress" (i.e. nerual processing associated with events that disturb homeostasis) influences the activity of the hypothalamus leading to activation of the HPA axis. -Most of the input from higher brain structures to PVN are form "limbic system".

Memory in Hippocampus: LTP and LTD

Relating LTP/LTD to memory: -learning about a place induces LTP in hippocampus. -LTP saturation produces memory deficits. -Manipulations that alter LTP/LTD impair hippocampal-dependent memory processes: -NMDA inhibition -monoamine inhibition -manipulations of epigenetic machinery

short-term regulation of energy: glucosostat hypothesis

Released from the pancreas: -low glucose - release glucagon -high glucose - release insulin "Glucostatic Hypothesis": -glucose levels are key target in short-term regulation of energy; i.e. defend specific glucose levels (or brain dies). -high glucose results in high insulin which acts on insulin receptors in brain that contribute to feeding regulation.

Simple systems approach again

Sensitization (non associative learning) in a simple system: -Instense stimualtion (shock) of head will activate L29 which produces a hyper-resposnive gill-withdrawal reflex. In sensitization of gill-withdrawl reflex, critical change is modification of presynaptic (i.e. sensory neuron) release of glutamate: due to L29 5HT (serotonin) --> increased active PKA (protein kinase A) --> decreased potassium channels.

temporal aspects of memory

Sensory information is detected and processed including the formation of conscious perception of the situation. Short-term = minutes to hours; a.k.a. working memory ~ active information buffer "held in mind". Long-term = relatively permanent (i.e. not forgotten); requires "consolidation" i.e. a long-lasting change in neuron function. Relation between short- and long-term memory is unclear.

Coordinated autonomic action: sex

Sexual behavior requires coordination of parasympathetic and sympathetic NS. -parasympathetic NS is activated during sexual arousal. -sympathetic NS is activated during orgasm.

Aspects of sexual behavior

Sexual drive (non-homeostatic) -locating a mate -overcoming obstacles to mating -mate recognition -sexual partner preferences -courtship behavior -copulatory parameters

Brain systems

So far, we have explored input and output for the brain/cortex, now we will explore the systems that coordinate brain function/states as well, that store info and evaluate the importance of info (motivation and emotion)... which are used to inform decision making

Steroid receptors ("classic mechanism")

Steroid receptors act as transcription factors i.e. change protein levels... long-term effects

Distribution of estrogen receptors

Steroid receptors are found in the brain (as well as throughout the body). -more estrogen receptors in hypothalamus and pituitary

Effect of estrogen on dendrites

Steroids affect neural plasticity (e.g. synapse maturation)

Steroid modulation of neurotransmitter receptors

Steroids and/or their "active" metabolites can impact neurotransmission by modulating receptor responses. "Neurosteroids" refer to steroids produced in the brain. e.g. allopregnanolone is a progesterone metabolite that modulates GABA-A receptors (similar effects as alcohol).

Steroids and brain organization

Steroids influence brain development to produce sex differences.

Lateral Hypothalamic Area (LH) and Feeding

Stimulating of the LH produces complex incentive-directed behavior. i.e. it has induced motivation to get food not just simple motor action such as chewing.

Autonomic Nervous system targets

Sympathetic and parasympathetic nervous systems regulate all other parts of the body; i.e. two body states Sympathetic and parasympathetic have opposite effects on targets. -Pre-ganglionic neurotransmitter is Ach for both sympathetic and parasympathetic nervous systems. -Post-ganglionic neurotransmitter is Ach for parasympathetic and NE for sympathetic NS. -Some targets are glands. Sympathetic activated during stress i.e. need energy fast; "fight or flight". Parasympathetic activated when relaxed; stores energy.

Limbic circuit connectivity

The Papez circuit first provided a framework for emotional expression/experience consisting of: interconnected limbic structures with extensive neocortical input and outputs from the hypothalamus.

Simple systems approach AGAIN

The critical determinant of conditioning is L29 5HT release coincident with SN activation to produce presynaptic plasticity (i.e. in SN). Note: use of a "modulatory" amine transmitter which is similar to induce a brain state via activation of diffuse modulatory system(s). But these effects are not long-lasting (i.e. last about 30 min) similar to "short-term" or "working" memory not "long-term" memory (e.g. days to weeks). In order for the conditioning-induced presynaptic plasticity to have permanent effects, there needs to be coordination why post-synaptic events: -NMDA receptor activation --> increased Ca++ --> increased Ca++ depolarizes kinases --> increase membrane AMPA (intermediate duration) --> increase in gene expression ("permanent").

Hippocampus encodes context information

The hippocampus adds contextual regulation, allowing you to distinguish the difference in threat level posed by a snake in the woods vs. in a zoo. -Hippocampus is important for encoding spatial information (i.e. how discreet environmental cues determine a "context").

Limbic inputs and outputs

The limbic system has extensive: -input from sensory association cortices (multimodal perceptual information) and prefrontal cortex (executive functions). -Output to prefrontal cortex influences conscious decision-making. -Output from hypothalamus to influence autonomic behavior and endocrine function.

PFC and cognitive control on emotional responses

The medial prefrontal cortex regulates the degrees to which the amygdala expresses fear responses. PFC which is involved in executive function (e.g. decision making) provides cognitive control over fear responding. -PFC also critical for the "relearning" that occurs during extinction training.

Dopamine and reinforcers

The mesolimbic dopamine (from VTA [ventral tegmental area] to several "medial limbic" structures) is crucial for reinforcement and operant behavior. Dopamine goes up during anticipatory phases of appetitive behavior. Dopamine goes up during aversive behavior. Mesolimbic dopamine is involved in goal-directed aspects of behavior but not hedonic aspects (reward); equivalent to "attention" or "incentive salience" signal. VTA dopamine is driving force for limbic/motivations system as SN is for basal ganglia.

context and motivation

The peeping monkey experiment: What does the monkey look at? Depends on internal and external factors. Incentive saliency refers to how important (salient) a stimulus (incentive) is at a given time.

Hormonal control of the ARC

The two types of ARC neurons have opposite responses to leptin and insulin. -NPY/AgRP neurons are inhibited by leptin and insulin. -POMC neurons (release alpha MSH and CART) are activated by leptin and insulin. NPY/AgRP and POMC neurons have reciprocal inhibition.

Sleep and brain activity

There are two major classes of sleep: 1) non-rapid eye movement (NREM) 2) rapid eye movement (REM). Transition between wake <--> NREM <--> REM is controlled by reticular formation: -Coordinated activation of Ach, (DA,) NE, 5HT diffuse modulatory structures to control brain activity -Overall brain activity is NOT decreased during sleep

Learning/memory, motivation, and emotion

These are distinct psychological processes that are central determinants of behavioral responsiveness. -Learning/memory = the storage and retrieval of prior events used to organize future behaviors. -Motivation = is the reason(s) for engaging in a particular behavior; include basic needs, desired objects, goals, or ideals. -Emotion = a mental and physiological state associated with a wide variety of feelings, thoughts, and behaviors.

Role of glutamate receptors in synapse plasticity

Three types of glutamate receptors are involved in memory. AMPA- gated sodium channel -NMDA- gated calcium channel -Metabotropic- Go coupled -NMDA- gated calcium channel and voltage-dependent (Mg++ block). -requires coincident extracellular glutamate and internal depolarization. -critical for many (perhaps all) types of learning.

Appetite vs. Aversive in the Brain

Ventral Striatum/nucleus accumbens (limbic output; a.k.a. limbic-motor interface) -activated for both good and bad -encodes salience (level of importance). -Medial PFC responds more to good than bad. -Lateral PFC responds more to bad than good. Suggests PFC is important for determining valency of stimuli

Peptide Hormones

What is the difference between peptide hormone and peptide neurotransmitter? Control of release and route to target cell; all other aspects (i.e. on "receiving cell") are the same.

Neural bases of motivation

Within the hypothalamus, there are structures specialized for homeostatic and non-homeostatic regulation of "motivation"; sets motivational "drives". A major target of several limbic structures is the Nucleus Accumbens (ventral portion of the striatum) which serves as an interface between limbic system (including hypothalamic drives) and motor systems.

Neural bases of motivation

Within the hypothalamus, there are structures specialized homeostatic and non-homeostatic regulation of "motivation"; sets motivational "drives" A major target of several limbic structures is the Nucleus Accumbens (ventral part of the striatum) which serves as an interface between the limbic system (including hypothalamic drives) and motor systems mediating incentive salience.

Circadian biological rhythms are endogenous

different levels of hormones throughout the sleep and wake cycle. endogenous = originating within an organism

ARC stimulation of feeding

low insulin and let in levels: NPY/AgRP neurons of arcuate nucleus: inhibit secretion of hormones controlling ACTH and TSH --> stimulate feeding behavior