Neuro Exam 4

Stress responses

What the brain/body does to meet stressors/challenges

Human Amygdala Responsively to Masked Fearful Eye Whites

When seeing a lot of whites of the eyes fear is triggered Produce fearful stimulus increasing amygdala response .017 seconds -> amygdala response

Hypothalamus is necessary and sufficient for the coordinate rage response

Without hypothalamus no rage With the hypothalamus but no cortex rage

Recency Effect

Words at the end of a list are still in short term memory

Parkinson's Disease - Causes

1 in every 100 >65 years old Very rare before age 45 Genetic and sporadic forms of the disease - Gene mutations: alpha-synuclein, Parkin, LRRK2, PINK1, DJ-1, ATP13A2 - Environmental: pesticide exposure

Changes in the brain - Neuropathology of depression is poorly understood

1. Decreased volumes (imaging and morphometric studies) - Hippocampus, amygdala, cortex - Glia and neurons 2. Changes of blood flow and metabolism - Frontal cortex, amygdala 3. Impaired HPA function and stress 4. Adverse impact on neurotrophic support, neurogenesis, cell survival

Schizophrenia; Neural Causes/Correlates? The dopamine hypothesis

1. Elevating dopamine in normal individuals produces schizophrenia-like positive symptoms 2. Increasing dopamine in schizophrenic individuals worsens symptoms 3. Blocking dopamine activity in schizophrenics reduces symptoms (antipsychotics) Some evidence for more dopamine receptors in the brains of schizophrenics, but results unclear

Etiology of Schizophrenia - two hit hypothesis Genetics

80-85% of having it with 50-100 susceptibility genes Neuregulin 1 (NRG1), disrupted-in-schizophrenia 1 (DISC1). dystrobrevin binding protein 1 (DTNBP1) Risk associated with biological parent NOT adoptive parents 2/3 neither first or second degree relative

Aphasia

A problem with language not intellectual development Not cognitive Impairment of language processing Disorder that impairs a person's ability to process language Most common cause is stroke (about 25-40% of stroke survivors acquire aphasia), but also caused by head injury, brain tumor or other neurological causes

Immediate memory

Ability to hold ongoing experiences in mind for fractions of a second Sensory impressions Proprioception

Memory

Ability to recall or recognize based on previous experiences, implies mental representation or memory trace

Schizophrenia: Neural causes/correlates

Abnormalities in prefrontal cortex, auditory regions (Broca's and Wernicke's areas) Thinned cortex in temporal regions Enlarged ventricles Less brain mass -> less brain activity Cerebral atrophy in temporal lobe, hippocampus, parahippocampal gyrus, amygdala Problem with neurogensis? Abnormal dendrites/disorganization in prefrontal cortex, hippocampus, entorhinal cortex Lower blood flow in prefrontal cortex and deficits in executive function -> decreased metabolism and activity ()

Locus Coereleus (norepinephrine neurons_

Activation by foot shock Respond to fearful stimulus

Anhedonia

Addicted subjects were found to have lower D2 receptor expression and lower baseline dopamine release Dopamine receptor change causes a blunted response to natural rewards such as food and sex Drug-induced dopamine overcomes baseline deficiencies Result: addicted subjects don't feel "normal" unless they have dopamine levels increased by their drug of choice

Right hemisphere Functions

Analysis of left visual field Stereognosis (left hand) Emotional coloring of language Spatial abilities Rudimentary speech

Left Hemisphere Functions

Analysis of right visual field Stereognosis Lexical and syntactic language Writing Speech

The problem with the monoamine theory

Antidepressants take weeks to become effective (even through the increase in 5-HT and NE occurs within days) Lowering levels of monoamines does not always produce depression Increasing levels of monoamines doesn't always alleviate depression

The limbic Lobe

Around Corpus callosum and diencephalon

Studying Learning: Instrumental Conditioning (Operant conditioning)

Association between actions and the consequence of those actions

Encoding

Attending to and linking new information to existing information already in memory

Second generation neuroleptics

Atypical antipsychotics, developed in the 1980s Clozapine, risperidone, olanzapine Fewer motor side effects, more effective at reducing negative symptoms A little more selective for D2 and don't have as many motor effects

Emotional Hypothalamus

Autonomic expression of emotions through activation of sympathetic system Expression of innate and conditioned defensive behaviors Specific changes in heart rate, temperature, sweating depending situation

Explicit Memory Storage

Bilateral temporal lobectomy Retained ability to form new implicit (procedural learning) memory

Opiates (morphine and heroin)

Bind to opioid receptors on the axon terminals of GABAergic interneurons Opiates are inhibitory - therefore decrease GABA release This disinhibits VTA neurons and increases dopamine release in the NAc

Nicotine

Binds ACh receptors on VTA neurons causing depolarization Increases glutamate release onto VTA neurons Both effects increase Dopamine release from VTA neurons projecting to the NAc

Cocaine and Amphetamine

Block the dopamine reuptake into VTA axon terminals Increases effect of dopamine in the NAc

Amphetamine has profound affects on synaptic dopamine levels

Blocks dopamine reuptake Amphetamine causes dopamine release Amphetamine reverses direction of dopamine transport Leads to huge increases in synaptic dopamine

Circumventricular Inputs to the PVN

Blood-borne signals

Stress: Hypothalamus-Pituitary-Adrenal Axis (HPA Axis)

CRH - corticotrophin releasing hormone ACTH - adrenocorticotrophin hormone Cortisol - stress hormone Results in alterations of serotonin (5-HT) and norepinephrine (NE) Hypothalamus receives information from the limbic system (emotion) from the senses (vision, auditory) and major organs (heart, stomach). hypothalamus secretes a hormone, CRH (corticotrophin releasing hormone). CRH enters the bloodstream for a short trip to the nearby pituitary Gland CRH stimulates the pituitary to release another hormone, ACTH (adrenocorticotrophin hormone), into the blood. ACTH travels to the adrenal gland where it stimulates the production and release of the "stress hormone," cortisol. Cortisol travels via the blood to several sites around the body - including back to the brain, promoting some functions and inhibiting others.

VTA to NA pathway

Caudate -> putamen -> nucleus accumbens -> VTA -> substantia nigra

Learning

Change in behavior as a result of experience (or practice or study!) Can be acquisition of information, behavior pattern or ability

How are memories stored in the brain?

Changes at the level of the neuron Changes in existing circuity

Movement Disorders

Characterized by abnormal movements Under or over activity

Tradive dyskinesia

Characterized by repetitive, involuntary, purposeless movements Mostly irreversible Thought to be postsynaptic DA receptor super sensitization

Schizophrenia: Treatment DA receptor antagonist

Chlorpromazine reduce POSITIVE symptoms Gradually effective over time (weeks) Side effects severely affect drug compliance - Many side effects related to changes in DA balance such as parkinsonism-like symptoms, tremors, akinesia, muscle rigidity, and tradive dyskinesia Second generation neuroleptics

Cortisol Under Production

Chronic fatigue syndrome, fibromyalgia, immune system rheumatoid arthritis, allergies, asthma

Normal Fear Reponse

Cognitive appraisal - Recognize and remember real threat Physiologic arousal - Signal danger - Enhance alertness - Prepare body for action Behaviors - Fight/Flight/Freezing

Feelings

Constructed from sensory feedback to the brain about emotional state Reflect a context-dependent cognitive process Shaped by exteroceptive cues Experience

MPTP

Contaminant in the production of synthetic narcotic IV drug users were presenting in emergency rooms with severe Parkinsonism overnight MPTP's mechanism of action was discovered to attack mitochondria Currently used in animal models Kills dopamine neurons very efficiently

Amphetamine/Cocaine Tolerance

Continued high-levels of synaptic dopamine activate dopamine auto receptors on the presynaptic neuron Autoreceptor activation inhibits production dopamine The neuron eventually becomes depleted of dopamine

Fear conditioning and memory require different brain regions

Controls individuals show appropriate fear responses to conditioned stimuli and no deficit in a memory task SM does not show appropriate fear responses to conditioned stimuli and no deficit in a memory task - Amygdala required for fear but not memory WC shows appropriate fear responses to conditioned stimuli and but major deficit in a memory task - Hippocampus not required for fear learning and required for memory

Problems with levodopa treatment

Converted to dopamine rapidly in the blood stream, so have to take fairly high doses High doses cause nausea and vomiting Long-term side effects: dyskinesias (involuntary, unwanted movements) and "on-off" periods (drug will unpredictably stop working and start working again Patients are treated with a combination of levodopa and carbidopa

Split-Brain Subjects

Corpus callous severed to help reduce epileptic seizure in small number of patients Since LANGUAGE functions are primarily located in left hemisphere, the left brain should be more "conscious" than the right brain

Addiction

Corruption of dopaminergic system extending from the ventral segmental area Addictive drugs "artificially" increases dopamine levels in situations that would normally have lower levels of dopamine Affects the perception/processing of reward Reinforce addictive behavior by increasing dopamine at the wrong time/circumstance

Forebrain inputs to PVN

Cortex Hippocampus Amygdala, bed nucleus Septum Thalamus

DRAW OUT Papez Ciruit

DRAW OUT Papez Ciruit

Hippocampus and spatial memory

Damage to perirhinal cortex disrupts the object recognition task shown in B, but hippocampal damage disrupts the object location task in C

ALS - Pathophysiology

Death of the upper and lower motor neurons - Motor cortex, brain stem, spinal cord Protein inclusions in cell bodies and axons of degenerating neurons -Protein inclusions can contain ubiquitin, SOD1, TDP-43, and FUS (Don't memorize list) Dark spots in cortical neuron: dark spots are clumps of proteins called inclusion which are sticky (resistant to being broken down); don't know if they are result or cause

Negative Symptoms of schizophrenia

Decreased motivation Diminished emotional recognition and expression (flat affect) Social withdrawal Poverty of speech

Anterograde

Deficit in learning new information

Retrograde

Deficit in recalling previous information

Parkinson's Disease - pathophysiology

Degeneration of dopaminergic neurons of the substantial migration pars compacta -Other neuronal populations degenerate including locus coeruleus Protein inclusions called Lewy bodies - Lewy bodies are found elsewhere including the olfactory bulb, medulla oblongata, and pontine tegmentum - In late stages of the disease levy bodies can also be found in the basal forebrain and neocortex

Deactivation of dopamine

Degradation and inhibition of MAO (monoamine oxidase - intracellular) and COMT (catechol-O-methyl-transferase - extracellular)

Memory Storage Sites: Karl Lashley and the "mass action principle"

Degradation of learning and memory depends on the amount of cortex destroyed NOT the type

How can we test declarative memory in animals?

Delayed non-matching-to-sample task

Positive symptoms of schizophrenia

Delusions Hallucinations Disorganized speech Paranoia Grossly disorganized behavior Overactivity of Dopamine

Tetrabenazine for chorea

Depletes stores of monamines by reversing the vesicular monoamine transporter 2 on vesicles Decreases dopamine release which reduces unwanted movement (basal ganglia)

Episodic memory

Detailed autobiographical memory

KNOPP Bioscience

Dexpramipexole - Phase iii clinical trial - Slowed disease progression - Increases mitochondrial efficiency to slow down neurodegeneration

Panic Attack

Discrete period of intense fear or discomfort accompanied by four or more of the following - Palpitations, trembling, chest pain, fear losing control, numbness, sweating, choking, dizziness, fear dying, chills/hot flashes Episodes have a sudden onset and peak rapidly (usually in 10 min or less) Often accompanied by a sense of imminent danger or doom and an urge to escape May present to ER with fear of catastrophic medical events Represents triggering of alarm response

Third generation neuroleptics

Dopamine stabilizer Ability Bind to Dopamine receptor and activates at a smaller degree Partial agonist at the D2 receptor - a partial agonist bins to the receptor and activates it, but to a lesser degree than the neurotransmitter (max effect is lower) (pPrevents DA binding; therefore preventing DA-induced maximum response) In areas of low dopamine, if stimulates receptors to raise the dopamine level therefore can reduce positive symptoms

Reserpine

Drug isolated from Indian snakeroot plant which has been used as an herbal remedy for thousands of years Depletes neurons of norepinephrine Preventing the loading of monoamine transmitters into synaptic vesicles, these depleting monamines

Treating Anxiety: Anxiolytics

Drugs that relieve anxiety Benzodiazepines: sedative hypnotics (CNS depressants) Diazepam (Valium) - GAD, PTSD, panic disorder Alprazolam (Zanaz) - panic disorder and GAD Relieve both psychological and physical symptoms of anxiety, help with insomnia Act quickly Tolerance can develop Risk of physical dependence and withdrawal, potential for abuse

Motivation

Emotional processing by the "limbic system" guides behavioral choices by signaling impending reward and punishment Dopamine signaling in ventral striatum (nucleus accumbens) important for reinforcement of behavioral movements -- more DA signaling increases motivation to perform these behaviors again in the future - DA inputs to nucleus accumbens = emotional reared circuit

Carbidopa

Enzyme that delays the conversion of levodopa to dopamine (how might this work?) Does NOT cross the blood-brain barrier Allows more levodopa to get to the brain, so lower does are required Inhibits dopa decarboxylase Produced a significant improvement in the treatment of PD Reduces nausea and vomiting associated with high doses of levodopa Other side effects are still present

Amygdala

Found in the temporal lobe adjacent to the hippocampus Responsible for relating sensory stimuli with emotional experience Site of associative learning Connections with cortex, hippocampus, hypothalamus, thalamus, basal ganglia

Semantic Memory

Generalized declarative memory

Etiology of Schizophrenia - two hit hypothesis Environment

Gestational and birth complications - Oxygen deprivation - Drug use - Viral infection during second trimester - Severe malnutrition - Birth during the late winter-early spring months Stressful childhood events - Exposure to toxins - Family climate - Socioeconomic status Cannabis use during adolescence - Functional polymorphism in COMT (affects availability of dopamine)increases risk for associated development of psychosis

Neural Circuit for Explicit Memories

H.M. pointed people to the hippocampus, but he had damage to many other regions as well Perirhinal cortex Parahippocampal cortex Entorhinal Cortex

Duchenne

Happiness produces a "duchenne smile" aka true emotional smile which cannot be faked and cannot be voluntarily produced Some muscle groups are " put into play by the sweet emotions of the soul"

Agent Orange

Herbicide used by the US military in the Vietnam war Exposure resulted in many health effects but has been linked to increased risk of developing Parkinson's disease

Hippocampal Place Cells

Hippocampal neurons that increase firing rates when the mouse walks/runs through a specific point in a previously learned maze Each new maze/circumstance leads to a new neural representation of space Spatial representations and sequences of activity are thought to be learned in hippocampal circuits Involves synaptic strengthening at CA1-CA3 synapses Underly learning of spacial relationships

Working memory (Short-term)

Hold info in mind forSeconds to minutes to achieve a goal Requires attention Hunting for objects Remembering a phone number until you can write it down

Depression: The monamine theory

Idea that clinical depression is due to blunted brain monoamine systems - serotonin (5-HT) and norepinephrine (NE) Evidence: Reserpine (antihypertensive and antipsychotic drug) - depletes 5-HT and NE, produces depression in ~10% "normal" people Antidepressants increase monamine levels and/or signaling (MAO inhibitors and SSRIs) Low levels of 5-HT in the brain ventricular fluid of suicide victims Decreased cortical activity in depression, especially prefrontal cortex

Cognitive Deficits

Impairments in executive function Attention Working memory Episodic memory Language comprehension Precede onset of psychosis

Elevated plus Maze

Inactivation of the amygdala (muscimol) causes decreased avoidance of open arms Without amygdala activity, the animals acts as if it reduced fear!

Benzodiazepenes Neurologic Function

Indirect GABA agonists Increase GABA binding Increase GABA effect No effect of benzodiazepines in the absence of GABA (makes them much safer than other drugs like barbiturates) Increased current with both GABA and diazepam (BDZ)

Fear Conditioning

Innate reflex (CR) is modified by associating the normal trigger stimulus (US) with an unrelated stimulus (CS) A neutral auditory tone (CS) is paired with a shock (US) The experience of the shock is related by the somatosensory system as "Pain" - negative reinforcement This association is "learned" by a strengthening of the auditory inputs through LTP This leads to better activation of amygdala circuits by the tone Enhances survival responses-freezing, changes in blood pressure

Emotional symptoms of Anxiety Disorder

Irrational and excessive fear or worry Panic Feelings of dread Trouble concentrating Irritability Feeling restless, tense, jumpy

Studying Learning: Pavlovian Classical Conditioning

Learning procedure whereby a neutral stimulus comes to elicit a response because its repeated pairing with some UCS, UCR, CS, CR Eye-blink conditioning

Language is Lateralize, Localized

Left frontal and temporal association cortices Broca's area Primary motor cortex Primary somatic sensory cortex Primary auditory cortex Wernicke's Area Primary Visual Cortex

Broca's Area

Left frontal lobe (Brodman areas 44, 45)

How can we study anxiety

Lesion different areas in animals Record from different brain regions during exposure to fearful stimuli Expose people to fearful stimuli and do brain imaging Give drugs that affect or mimic NT and look at behaviors

Deep Brain Stimulation

Location: Internal Globus Pallidus or Subthalamic nucleus Over-rides intrinsic pathological discharge patterns with stable, structured patterns Facilitates wanted movement Down sides: worsen depression, brain surgery, expensive

Korsakoff's Syndrome

Long term alcoholics Caused by a thiamine (vitamin B1) deficiency due to prolonged intake of large quantities of alcohol Characterized by both retrograde and anterograde amnesia Patients are generally indifferent to suggestions they have a memory problem Most patients show atrophy/decreased activity in the frontal lobe of the cerebral cortex (as wells parts of the thalamus and hypothalamus) Anterograde and Retrograde Memory

Other treatments of Parkinson's: prevent DA degradation after release

MAO-B inhibitor boost effects of levodopa and carbidopa - Controls metabolism of DA in the brain - Side effects: agitation, insomnia, and hallucinations COMY inhibitions prolong symptom relief by postponing metabolism of levodopa - More L-dopa reaches the brain, therefore raising the DA level - Provides a more stable, constant supply of L-dopa - Side effects; abdominal pain, back pain, constipation, nausea, diarrhea, liver failure

Peripheral Manifestations of Fight or Flight Response

Many signs explained by sympathetic nervous system activation and release of NE from adrenal medulla Increases in heart rate, blood pressure, ventilation, glucose Pupils dilate Sweating Piloerection

Storage

Mechanisms and sites by which memories are retained over time

Rotenone

Mitochondrial complex I inhibitor Was marketed as an "organic" pesticide due to its natural occurrence in roots and leafs of some plants Exposure has been linked to increased risk of developing Parkinson's disease Currently used in animal models

Other hypothalamic nucleus inputs to the PVN

Motivational and behavioral states (LH) Interoceptive context

Broca's Aphasia

Motor, "expressive" aphasia Problems expressing language Disruption of language production (finding/expressing the right words) and organization (grammar, syntax) Problems apparent with written, spoken, "signed" language Patients cannot produce speech, but CAN understand speech Patients are acutely aware of their problem

Huntingtons Disease - Symptoms

Motor: lack of coordination, unsteady gait, chorea Cognitive: executive functioning such as planning, abstract thinking, rule acquisition Mood: anxiety, depression, reduced display of emotions

ALS - Symptoms

Motor: muscle weakness, tripping, dropping items, fatigue, slurred speech, muscle cramps End stages: impact muscles responsible for breathing which leads to ventilator use Steven Hawking and Lou Garig

Schizophrenia; Neural Causes/Correlates? The Revised dopamine hypothesis

Negative symptoms and cognitive impairment - Deficit in prefrontal DA (hypo stimulation of D1 receptors) - Associated with defects in a subset of GABAergic interneurons Positive symptoms - Excess subcortical DA (hyper stimulation of D2 receptors)

Role of Synapses in Learning and Memory - Neuroplasticity

Nervous system's potential for neurophysical or neurochemical change that enhances its adaptability to environmental change and its ability to compensate for injury

Classic Hypothalamus

Neuroendocrine function through connections with the pituitary gland Sleep/wake circadian rhythms Feeding and breeding

Schizophrenia

Neuropsychiatric disease (Kraeplin 1887) Schizophrenia: patient is detached from relation (split mind by Bleuler) Over-represented among homeless, incarcerated, and unemployed Affects both genders equally Onset between 15 and 30 years old 4-5 years earlier in males 20-50% attempt suicide, 4-13% complete suicide

ALS - Treatment

No Cure Focus on improve quality of life - Riluzole can extend the amount of time before ventilation support is needed and it can extend survival by a few months - Medication can be used to help reduce side-effects - Physical Therapy

Parkinson's Disease - treatment

No cure Motor symptom relief: L-DOPA, DA agonists, MAO inhibitors Deep Brain Stimulation Exercise

Huntington's Disease - Treatment

No cure Treatments for symptoms - Tetrabenazine for chorea - Physical Therapy

ALS - Causes

Onset: 60 yrs - 5600 diagnosed every year - 20% more common in men than women 5-10% inherited, the rest sporadic - Superoxide dismzutase (SOD1) mutation 20% of familial ALS cases - Environmental Factors: military veterans deployed during the gulf war are twice as likely to develop ALS

Huntington's Disease - Causes

Onset: middle age Poly-Q repeat in the N-terminus of huntingtin protein - CAG nucleotide repeat that codes for the amino acid glutamine - Does not fold correctly, making it very sticky - Healthy if <36 repeats - Symptomatic if >40 repeats Gene mutation is autosomal dominant

Physical Stress Responses

Overall effect is to INCREASE CATABOLIC and DECREASE ANABOLIC processes Hypothalamus: endocrine, autonomic, behavioral components Specifically the PVN

Nigrostriatal

PATHWAY ROLE DOPAMINE

Hypokinetic

Parkinsonism, apraxia, catatonia, gait disorders, stiff persons Under activity and lack of movement

Amnesia

Partial or total loss of memory

When Anxiety Becomes Pathological

Pathological anxiety occurs when safe stimuli acquire a meaning of danger Anxiety is excessive, inappropriate or generalized Responses to feared stimuli are maladaptive Becomes a DISORDER when source of significant subjective distress or functioning impaired

Sites where electrical stimulation interferes with speech production

Penfield: Shows Broca's and Wernicke's area PET: positron emission tomography (brain activation) -Viewing the word = visual -Listing to word = temporal -Speaking word = Motor -Association = Broca's and Wernicke's

Cons of Human Subjects

People don't like being poked Need to be very sure you aren't going to hurt them Humans are very complex, and have several variables to account for Can't determine mechanism so easily

Patient S. M. Bilateral lesions of the Amygdala

Physically unable to feel fear Cannot recognize fear in facial expressions Does not have a concept of personal space Does have startle response that does not depend on the amygdala Can follow group fear responses due to voices and body responses in others Has survived physical abuse and had a knife held to her throat

Emotional State

Physiological state Product of endocrine, autonomic, somatic output systems Emotional motor system Product of innate and learned responses to external stimuli and internal thoughts Subconscious

Physical symptoms of anxiety disorder

Pounding heart Sweating Shortness of breath, choking Muscle tension Headaches Fatigue Insomnia

Test after long delay

Primacy

Parkinson's Disease - Symptoms

Primary Motor: resting tremor, bradykinesia, fidgety, postural instability Secondary motor: loss of automatic movements, speech changes, flat affect, writing changes, bp regulation Non-motor: loss of sense of smell, REM behavior disorder, mood disorder, orthostatic hypotension, depression, dementia

L-DOPA

Primary treatment is to give Dopamine precursors Levodopa Can cross blood brain barrier Developed in the 70s still considered the gold standard of PD treatments Mechanism of action? - converted into dopamine in the brain - released by remaining dopamine neurons Why not just give dopamine? - Can't cross blood brain barrier

Non-declarative Memory

Procedural: things you know that you can show by doing Motor skills Associations Priming cues Puzzle-solving skills

Retrieval

Process by which stored information is recalled Most effective when cued

Consolidation Definition

Process that converts short-term memories to long-term memories Requires changes at the level of genes and proteins Enhanced by practice

Anterograde Amnesia

Profound loss of short term declarative memory, unable to consolidate new long-term declarative memories

Paper Circuit

Proposed Circuit for emotional processing Main Pathways to the hypothalamus Consists of Cingulate cortex, fornix, thalamus, mammilary bodies, hippocampus Missing amygdala, frontal cortex (emotional centers)

Role of Right Hemisphere

Prosody: coloring of speech Includes the rhythm, timing, emphasis, volume, tonal (pitch) variations of verbal speech Conveys emotion and grammatical emphasis

Huntington's Disease - Pathophysiology

Protein inclusions -Contain mutant forms of huntingtin protein Neurodegeneration of the caudate and putamen

Autonomic nervous system controls physiological CALMING

Pupils contract Salivatoin increases Skin dries Resperation decreases Heart rate decreases Digestion activates

Wernicke's Area

Rear left temporal lobe (Brodmann area 22)

Test after short delay

Recency and Primacy

Immediate Test

Recency effect

Reward synapse

Reinforcement system with homeostatic input Ventral tegmental area to nucleus accumbens Innervation with motor loop to physically complete the action Innervation with learning and memory since this is the place with the resources to return to homeostasis Additional higher level processing (frontal cortex) for options

Role of Synapses in Learning

Relatively permanent change in behavior that results from experience Mediated by structural changes in synapses

The hypothalamus coordinates the visceral and somatic motor components of emotional behavior: Sham rage

Removed both cerebral hemisphere, underlying white matter and the basal ganglia After anesthesia wore off, the animals acted enraged - Autonomic correlates: increased blood pressure and heart rate, dilation of pupils, piloerection - Somatic components: arching the back, extending claws, snarling/ hissing Occurred spontaneously

Consolidation

Requires the hippocampus and adjacent parahippocampal (rhinal) cortex Requires repetition

Long-term Memory

Retaining information for days, weeks, life Retaining information of particular importance (for your exam) Retaining salient events, skills...

Wernicke's Aphasia

Sensory/receptive aphasi Language produced, sounds normal, but much of it makes no sense Many patients seem to be completely unaware of their problem

Emotional Paresis

Smile full way voluntary Smile half way involuntary Descending extrapyramidal projections from medial forebrain and hypothalamus

Facial Paresis

Smile half way voluntary Smile full way involuntary Descending pyramidal and extrapyramidal projects from motor cortex and brainstem

Auditory flow

Spoken word -> A1 (primary auditory cortex) -> Wernicke's area (contains sound images of words) -> Comprehend word heard

Mesolimbic

Starts in midbrain and goes to the limbic system Main reward pathway in the brain "Do it again" pathway Promotes survival

Primacy Effect

Subjects are better at remembering words at the beginning of the list

Implicit Memory Storage : Patient J.K.

Suffered from Parkinson's disease Dysfunction of the basal ganglia Demonstrated disruptions in motor tasks or types of memory that seemed implicit Perfectly intact episodic and declarative memory Storage must be in different places

Pros of Human Subjects

Tell people what to do Easy to understand results Immediately applicable to helping human conditions Understand human phenotypes

Delayed non-matching-to-sample task

Test of object recognition memory that requires monkeys to declare what they remember Monkeys must identify what was not seen previously, over a range of delay times Medial temporal lobe damage, similar to Henry's, causes impairment on this task

Learning to Memory

The transition from learning to memory involves a long-term adaptation of circuits Generally memories are formed by increasing the strength of synapses responsible for mediating the new behavior or storing facts

Stressors

Things that challenge homeostasis Real or merely anticipated

Declarative Memory

Things you know that you can tell others Daily episodes Words and their meanings Histroy

Information Flow of language

Thought -> Wernicke's area (THIS IS WHERE CONNECTION IS LOST)-> Broca's area (stores motor program from speaking works) -> Facial area of motor cortex -> cranial nerves -> speak

Episodic memory: Patient K.C.

Traumatic brain injury resulting from a motorcycle accident Cognitive abilities normal, short-term memory intact Can recall facts about himself but has NO memory of events that included him: EPISODIC AMNESIA Often associated with damage to the frontal lobe of the cerebral cortex Cannot retrieve personal memory due to accidental damage to the cortex Hippocampal damage accounts for his anterograde amnesia but not for the loss of autobiographical memory

Hyperkinetic

Tremor, dystonia, chorea, tics, myoclonus Over activity and to much (unwanted) movement

Dopamine pathway

Tyrosine -> tyrosine hydroxyls -> L-Dopa -> Dopa Decarboxylase -> dopamine

Parkinson's Disease - research

Understanding the causes and mechanisms of degeneration - Development of animal models that replicate the features Discovering better treatments and therapeutics - Stem cell therapy: transplant of stem cells that have been differentiated into neurons into the substantial nigra -Gene Therapy: viral medicated delivery of genetic material into the brain

ALS - Research

Understanding the causes and mechanisms of degeneration in ALS - Gene sequencing to better understand causes underlying ALS Discovering better treatments and therapeutics - Clinical trials with drugs - Stem cell therapy

Huntington's Disease - Research

Understanding the causes and mechanisms of degeneration in Huntington's disease - Mechanism of mutant Htt Discovering better treatments and therapeutics - Drug development to protect degenerating neurons - GENE SILENCING: allele specific silencing to shut off the mutant form but maintain the wild-type form -Stem cell therapy to replace degenerated neurons

H. M.

Underwent bilateral medial temporal lobe surgical resection at age 27 - Portions of amygdala, hippocampus, and underlying temporal lobe (rhinal cortex) removed bilaterally to control epileptic grand mal seizures Surgery was successful to reduce seizures No loss of I.Q. No apparent personality changes Could form procedural memory Remembered everything from previous life Anterograde Amnesia

DA Neurons in the VTA change their activity patterns during reward learning

VTA neural response to an unexpected juice award After learning, VTA neural responses to the cue that predicts the impeding juice reward When juice reward is predicted but not delivered, VTA neural activity is suppressed VTA goes quiet when reward is not given after the conditioned stimulus

Brainstem Inputs to the PVN

Visceral sensory Somatic Nociceptive Special Sensory

Long term synaptic plasticity

change in synaptic strength that lasts minutes to days to years Long Term potentiation - increase in synaptic strength Long term depression - decrease in synaptic strength Occurs in DG-CA3 and CA3-CA1 synapse

Conduction aphasia

damage to fibers (arcuate fasciculus) linking Wernicke's and Broca's ares Patients have problems production appropriate responses to language even though the language is understood Characterized by poor speech repetition Patients seem to lose their train of thought due to lack of communication between Wernicke's area (sound/meaning) and Broca's area (motor commands)

Used to see in the Brain

fMRI EEG MEG DTI But in the 19th century: sit and wait for someone with brain damage to come along

Autonomic nervous system controls physiological AROUSAL

pupils dilate Decrease salivation perspires Increase resperation Accelerate heart reate Inhibit digestion Norepi and epi