Neuro II Exam II

What are the 3 functions of CamKII?

- Phosphorylation of AMPARs to increase conductance - Increase AMPARs inserted into membrane - Phosphorylates stargazin on AMPARs to immobilize them into the membrane

What are some kinds of nondeclarative memory and where do they manifest in the brain?

- Procedural memory (striatum) - Classical conditioning (cerebellum) - Emotional response (amygdala)

Describe the phases of classical conditioning

1) Acquisition: CS and UCS both increase strength of the CR 2) Extinction: The CS decreases strength of CR 3) Extinction after a pause: Spontaneous recovery of CR strength relative to the CS but then extinction follows

How do you test whether or not LTP is synapse specific? What will the results show?

1) Establish baseline EPSP from 2 different inputs onto 1 postsynaptic cell 2) Tetanus on input 1 but no for input 2 3) Measure EPSP for each input Results: EPSP increases for 1 but not for 2. This occurs because of many factors but mainly the Mg++ plug being removed from the NMDA receptors so Ca++ can flow through

What are the two key principles fo LTP?

1) LTP is synapse specific 2) Co-active synapses cooperate to induce sufficient depolarization

Describe the mouse experiment steps for introducing false memories during reconsolidation with contextual fear conditioning

1) Label active neurons with Channelrhodopsin 2 2) Reactivating the memory and altering it 3) Testing if memory was altered 4) Testing if fear is generalized Shows by activating specific neural networks that encode a memory you can perturb them and change the memories themselves

Describe how long-term sensitization works in aplysia

1) Larger/more tail shocks allows for more serotonin release onto sensory neurons 2) PkA increase closes K+ channels but a lot more pKA. PkA also activates CREB via phosphorylation. 3) Phosphorylation of CREB triggers a cascade of effects in the presynaptic neuron to promote synaptic consolidation in sensitization and leads to synaptic growth

What are the steps of spine enlargement?

1) Spine gets bigger: Calpain deconstructs original shape, AVC provide more membrane insertion, CamKII rebuilds and stabilizes 2) Recycled vesicles insert new AMPA receptors into new membrane 3) The polyribosomes make proteins and our synaptic tag captures them which expands post-synaptic density 4) Creates larger presynaptic density which allows for more release of glutamate

Describe the sensitization mechanism in Aplysia Californica

1) The axon terminal of the siphon sensory nerve has metabotropic serotonin receptors. Serotonin from the facilitatory neurons is released and binds to these receptors 2) These receptors are coupled to G-proteins binding of serotonin stimulates production of cAMP 3) cAMP binds to the regulatory subunits of protein kinase A which then liberates the catalytic subunits of pkA 4) The catalytic subunits are then able to phosphorylate several proteins. One such protein is the S type K+ channels which undergo conformational change when phosphorylated to close its receptor. When S type K+ channels close they cannot participate in repolarizing the membrane terminal 5) This prolongs the action potential and thereby opening more Ca++ channels 6) The increased Ca++ influx causes enhanced glutamate release onto postsynaptic motor neurons which results in larger EPSP in the postsynaptic motor neuron

Describe the habituation mechanism in Aplysia Californica

1) Transmission at the glutamatergic synapse between the sensory and motor neurons is depressed which causes a decreased ability of siphon stimuli to induce gill contractions 2) This causes a reduction of the number of synaptic vesicles available for release and inactivation of voltage dependent Ca++ channels which leads to decreased amplitude of motor neuron EPSP

What is classical conditioning?

A previously neutral stimulus begins to elicit a response after pairing it with a stimulus that evokes an automatic response

Describe the delay versus no delay experiment that measures spatial working memory

A radial arm maze was used with two types: - No delay: Tests hippocampal memory and to some extent working memory - Delay version: Tests the limits of working memory

What is ARC and what does it do?

ARC is an intermediate early gene that promotes changes to the dendritic spine to promote LTP. ARC localizes to the actin cytoskeleton and phosphorylates structural proteins in the spine

Describe how LTD occurs

Active during weak depolarization causes LTD. Prolonged tetanization of Schaffer collaterals at low frequencies leads to LTD: low level activation of NMDARs, small Ca++ influx, weak depolarization. It disrupts the equilibrium of AMPARs

How is sensitization induced in aplysia?

After tail shock, serotonin is released onto the presynaptic terminal of the sensory neuron. This closes this closes the S type K+ channels

Karl Lashley studied the effects of various-sized cortical lesions on maze performance in rats. He concluded that the memory deficits were correlated with the size of the lesion but not the location and hypothesized that all cortical areas contribute equally to learning and memory. What is the current interpretation of these experiments?

All cortical areas do not contribute equally to memory, but memories are widely distributed

What is learning?

An enduring change in the mechanisms of behavior involving specific stimuli/responses that results from prior experience

Why are NMDA receptors often called coincidence receptors?

Because it detects postsynaptic depolarization as well as presynaptic glutamate release

How is a mechanism of behavior different than behavior?

Behavior can be determined by many factors but a mechanism of behavior shows that the environment must be conducive to show behavior.

How does the relationship between NMDA and calcium affect LTP?

Blocking NMDA or calcium = No LTP = No hippocampal dependent learning NMDA receptor activation is needed for the induction of LTP and acquisition of contextual fear memory

What is required for long-lasting enlargement?

CAMKII is required for long-lasting spine-enlargement because it stabilizes the enlarged structure

Why did the hippocampus lesion impair freezing in Context B (Sunset Room) but not Context A (Wilshire Room) in the Anagnostaras paper?

Context A (Wilshire Room) was used as the remote contextual fear memory and Context B (Sunset Room) served as the location for developing the recent contextual fear memory. Past studies have also shown that hippocampal lesions can cause retrograde amnesia. Thus, the lesion impaired freezing in Context B but not Context A because the memory in Context B had no time to consolidate. So the rat could remember the non-declarative memory from context A but not the declarative memory from Context B.

Which type of memory can be accessed for conscious recollection?

Declarative memory

What are some difference between early and late LTP?

Early: changing conductance: phosphorylation of AMPARs, insertion of more AMPARs, immobilization of AMPARs Late: Physically changing synapse: induction of gene transcription and protein synthesis = morphological change in shape of the synapse, phosphorylation of CREB

What is the behavioral measure of fear in the Anagnostaras paper?

Freezing behavior

What type of receptors are serotonin and glutamate?

Glutamate -> Ionotropic Serotonin -> Metabotropic

What are entorhinal grid cells and what do they do?

Grid cells fire in multiple[ areas of space and they fire periodically as a function of absolute distance. the grid fields become larger as you move ventrally through the entorhinal cortex

Which is stimuli specific, habituation or sensitization? Explain

Habituation is stimulus specific, weak stimuli habituate easier than strong stimuli, if you keep changing stimulus you wont get habituation Sensitization is not stimuli specific, it is usually thought to be produced by strong stimuli

What happened to HM?

He had most of his hippocampus and other medial structures removed. He later developed anterograde amnesia where he could not form new declarative memory. His remote memories were there but his recent ones were not

How does cooperativity relate to memory?

Helps form associations between different aspects of an experience. If many synapses are activated together to induce LTP then later on, if even one fires the memory will still be brought back

What are place cells and what do they do?

Hippocampal cells have spatial receptive fields which fire only when the animal is only when the animal is in a specific location. They can also remap their field if the environment changes

What medial temporal lobe structures are important for declarative memory consolidation?

Hippocampus, parahippocampal and rhinal cortical areas, fornix

What is one explanation of why classical conditioning works?

If two inputs are on the same neuron are individually stimulated, then the weak one can benefit from the protein synthesis of the strongly stimulated one

What is the difference between classical and operant conditioning?

In classical conditioning the subject does not control the response/outcome, the stimulus merely becomes predictive of behavior. In operant conditioning the subject must act on their environment to get an outcome

What is operant conditoning?

Individual learn to associate a response with a meaningful outcome

What is proven by spontaneous recovery in classical conditioning?

It proves that extinction is not unlearning/forgetting, it is the learning of a new association

What is one of the main things late LTP phosphorylates? Expand on this

Late LTP involves persistent phosphorylation of CAMKII -> CAMKII can autophosphorylation and thus CAMKII activity persists well after Ca++ levels have returned to baseline. Then activation of intermediate early genes induces transcription factors that facilitate long-term memory (late LTP)

Neural recordings in human medial temporal lobe have uncovered cells selective for what ?

Low-level visual stimuli

What is cooperativity?

Many presynaptic inputs are simultaneously stimulated to cause spatial summation of EPSP

What were Hebb's conclusions?

Memories are widely distributed through connections linking neurons in an assembly. Thus, destruction of just part of the assembly doesn't eliminate all memory

According to research in monkeys using the delayed-match-to-sample task, hippocampus is needed for retaining memory ... ?

More than about tens

What are some changes in behavior that aren't changes in learning?

Motivation, fatigue, maturation

What is multiple trace theory? Standard theory?

Multiple trace theory describes how memories are distributed in networks and each time you recall that memory you then get an overlay of new networks. Standard theory describes how over time, the entire memory trace gets moved from the hippocampus to the neocortex

Is multiple trace of standard theory more likely? Why?

Multiple trace theory. Evidence is given by the case of HM who could recall some remote memories and couldn't recall other remote memories

What is the general cellular basis for learning?

Neurons develop response selectivity over continued presentations of a set of stimuli. This transformation of responses is due to changes on the strengths of connections between neurons in a network.

How did Hebb define the cell assembly?

Neurons simultaneously activated by an external stimulus that are reciprocally interconnected

Will LTP and LTD go on forever once stimulates? Explain

No; Plasticity occurs due to Ca++ influx and eventually that influx runs out so LTP and LTD will end until stimulated again

Which kind of learning involves a change in behavioral response that occurs over time in response to a single type of stimulus?

Non-associative

What is non-associative learning and what are two forms of it?

Non-associative learning is a change in a behavioral response that occurs over time in response to a single type of stimulus two types are habituation and sensitization

Are memories hippocampal dependent?

Not exactly; recall of memories is often initially dependent but systems consolidation allows for non-hippocampal dependent recall

Bilateral temporal lobectomy such as that sustained by H.M. is characterized by which of the following?

Permanent anterograde amnesia but intact procedural memory

Why is strong stimulation required for persistence of LTP?

Persistence of LTP requires synaptic stimulation strong enough to trigger protein synthesis in the postsynaptic neuron

Describe why persistent activity is important for working memory

Persistent activity temporarily holds information for predicting and planning the saccade to the target. Neurons that are active during the delay fire to targets in specific locations. Therefore, the persistent activity of a neuron is encoding the location of a target.

What does the cellular mechanism for working memory involve?

Persistent activity/firing of PFC neurons

How does CREB impact memory consolidation?

Phosphorylation of CREB affects protein synthesis and memory consolidation. CREB 1 increases gene expression when phosphorylated by pKa (strengthen memory). CREB 2 represses gene expression when it binds to CRE (blocks memory consolidation).

How are entorhinal grid cells and place cells related?

Place cells receive input from grid cells w/ similar spatial phase but a diversity of spacings and orientations. Summing grids with varied periodicity will result in peak activity in the area where the grids overlap.

What is the main thing that is required for LTP to occur?

Presynaptic and postsynaptic must be active at the same time because the Mg+ plug will not be removed unless the postsynaptic cell is very depolarized

What is synaptic scaling? Expand

Process where the absolute synaptic effectiveness is adjusted to preserve homeostatic synaptic weight. CaMKIV induces the removal or insertion of both NMDARs and AMPARs to balance activity. Relative synaptic weights are maintained.

Memory required for animals to behave successfully in the delayed non-match to sample (DNMS) task is which of the following?

Recognition memory

What term best describes the process by which reactivating a memory makes it sensitive just as it had been immediately after the memory was first formed?

Reconsolidation

What occurs when a memory is reactivated and reconsolidated?

Retrieving a memory reactivates the memory trace in the neurons, this reconsolidates the memory but both processes makes the memory unstable and vulnerable to change

How is spine enlargement impact postsynaptic density?

Spine enlargement increases postsynaptic density. Cytoskeleton collapse causes the spine to change its shape to one that has more surface area and volume. This allows for more APARs to be inserted into the postsynaptic membrane.

Do neurons store memory or synapses? Explain

Synapses; a unique pattern of connection across a given group of cell store each unique memory (distributed memory)

How do we induce sufficient post-synaptic depolarization?

Temporal summation of EPSP or spatial summation of EPSPs (cooperativity)

What is the hippocampus and what input does it get?

The hippocampus is a brain structure that receives highly processed sensory information mainly from the entorhinal cortex

What is a dendritic spine? What does it have to do with LTP?

The point on a dendrite where contact is made with a presynaptic cells axon. LTP is associated with changes in spine shape (bigger after LTP)

What does it mean to say reactivates memories are unstable?

The reactivates and reconsolidated memories are unstable and vulnerable to behavioral/psychological change as well as tissue damage. Ex) Veterans were tested for PTSD symptoms, half with no treatment, half with stuff that blocks reconsolidation. Those who had the blocked reconsolidation experienced less PTSD symptoms

Why did the researchers feel it was important to compare recent and remote fear memory using a within-subject design (that is, within the same subject) in the Anagnostaras paper?

The researchers felt it was important to compare a recent and remote fear memory using a within-subject design because of the plethora of confounding variables there could be. One such variable is that there is a lot of variability in the levels of hyperactivity produced by the hippocampal lesions. By using a within-subject study the finding of the loss of the recent contextual fear can't be soiled by a confounding variable such as hyperactivity level influenced freezing response. So, a within-subject study is more ideal than the between-group studies that have been previously conducted by other researchers.

What is metaplasticity? Expand

The threshold for LTP changes depending on the history of activity. It is mediated by the subunit composition of NMDAR. MR2B is more LTP and NR2A is more LTD.

Describe how the neuronal firing varies during initial response and during the delay period in a delay match to sample task

There is low cell firing in response to the visual stimulus initially but there is activity. However the cell fires an incredible amount during the delay period, especially in areas that were not stimulated as much during the initial periods

T or F: Working memory is limited in capacity

True; it requires active rehearsal

Efficient performance in the standard radial arm maze (never going down the same arm twice) appears to depend on which type of memory?

Working Memory

What is working memory and where is it stored?

Working memory is sensory information that is held after the sensory stimuli are gone. Most information held in working memory is lost as soon as attention is directed elsewhere. It occurs in the prefrontal cortex and the lateral intraparietal

What kind of working memory is LIP most likely to be involved in?

Working memory that involves eye movements

What is sensitization?

a strong salient stimulus results in an exaggerated response to all subsequent stimuli

What is positive punishment?

adding a stimulus to stop a behavior from happening ex) not shocked if food lever is pressed

What is positive reinforcement?

adding something into the situation that increases the tendency to repeat the preceding behavior ex) getting dessert if you eat your veggies

What is synaptic consolidation?

changes in neurotransmitter release, gene transcription, protein synthesis, and morphological structure of the synapse to maintain memory

What neurons are persistently active during delays?

d1PFC and LIP neurons (LIP neurons encode for the location of target during the retention interval)

What is negative punishment?

removing a stimulus to stop a behavior from happening ex) no TV if your fight with your siblings

What is negative reinforcement?

removing stimulus to increase likelyhood of behavior being repeated ex) no chores if you eat your veggies

What is habituation?

repeated presentation of the same stimulus produces a progressively smaller response

What is the law of effect?

responses that are satisfying are more likely to be replicated in that context, responses that are aversive are less likely to be repeated