Cellular Mechanisms of Learning and Memory

Question 1

Memory is broken down into two major categories; declarative and nondeclarative memory. Describe declarative memory:

Answer 1

Declarative memory is the storage & retrieval of material that is available to consciousness and can in principle be expressed by language (e.g., declared as phone # s, words to songs, or a past event). It includes daily episodes, words and their meaning, and history.

Question 2

Memory is broken down into two major categories; declarative and nondeclarative memory. Describe nondeclarative memory:

Answer 2

Nondeclarative (or procedural) memory is not available to consciousness, and involves skills or associations that are acquired & retrieved at an unconscious level (e.g., how to use your phone, how to sing a song). Includes: motor skills, associations, priming cues, puzzle-solving skills

Question 3

Who was patient H.M. what did he suffer from, what did they do to try to relieve his suffering?

Answer 3

Patient H.M. suffered from intractable epilepsy. He underwent bilateral resection of much of his hippocampus and medial temporal lobe. His epilepsy was cured but his ability to form certain memories was lost.

Question 4

Post surgery what happened to H.M.?

Answer 4

Following surgery, his epilepsy was relieved and H.M. appeared normal. He had a normal I.Q., normal short-term (working) memory, and normal memory of events that took place before the operation. However, he could no longer form memories of events that took place after his operation.

Question 5

H.M. could no longer form memories after his surgeries, except one type of memory, what was it?

Answer 5

Tests indicated that H.M. could form certain types of memory (called PROCEDURAL or REFLEXIVE memories). He practiced drawing a star inside the lines for 3 days and got better over time even though he had no recollection of doing the task before. Only his declarative memory was impaired.

Question 6

What happened to patient R.B.?

Answer 6

Following bouts of anoxia due to cardiac arrests, another patient, R.B. exhibited similar but more modest memory impairment compared to H.M.
Autopsy revealed specific bilateral brain damage to area CA1 of the hippocampus

Question 7

Spatieal learning and memory depends on what structure in the brain? How was this proven?

Answer 7

The hippocampus. This was proven in rats in a tub of opaque water with a hidden platform below the surface. After a few trials, normal rats rapidly reduce the time required to find the platform, whereas rats with hippocampal lesions do not.

Question 8

What are the brain areas associated with declarative memory disorders?

Answer 8

Hippocampus, Thalamus, fornix, rhinal cortex, amygdala, mammillary body, prefrontal cortex, basal forebrain

Question 9

What is working memory?

Answer 9

Working memory is the ability to hold & manipulate information in mind for seconds to minutes while it is used to achieve a particular goal (e.g., searching for a lost object; it is called short-term memory). It is limited in duration & capacity.

Question 10

Describe the acquisition and storage of declarative memory: Where is the short-term memory storage and the long-term storage?

Answer 10

Short-term is in the hippocampus and related structures. Long-term is a variety of cortical sites: Wernicke’s area fro the meanings of words, temporal cortex for the memories of objects and faces, etc. Acquisition and storage of declarative memory is thought to require hippocampus and related structures and be transferred to cortical structures for long-term storage (consolidation)

Question 11

Describe the acquisition and storage of nondeclarative memory: Where is the short-term memory storage and the long-term storage?

Answer 11

Short-term storage sites are unknown but presumably widespread. Long-term storage is in the cerebellum, basal ganglia, premotor cortex, and other sites related to motor behavior.

Question 12

What is required for there to be long-term memory?

Answer 12

The physical embodiment of long-term memory, the ENGRAM, depends on long-term changes in the efficacy of synaptic transmission (e.g., growth and/or reordering of relevant synaptic connections).

Question 13

What structures are required to form declarative memory?

Answer 13

The hippocampus, medial temporal lobe structures, and midline diencephalic regions are important for declarative memory.

Question 14

What is Long Term Potentiation (LTP)? What type of memory does it model and where?

Answer 14

It is a long-lasting increase in synaptic strength that provides and attractive neural mechanism for certain forms of learning and memory. LTP is a model for declarative memory. LTP is commonly examined at Shaffer collateral-CA1 synapses in hippocampus. Pyramidal CA3 neurons in hippocampus send axons (Schaffer collaterals) to synapse on pyramidal CA1 neurons.

Question 15

How do NMDA and AMPA receptors used in LTP production work?

Answer 15

The NMDA receptor needs a high-intensity high-frequency stimulation to remove the Mg and create a signal. The AMPA receptor is much more simple and can be activated by low-frequency and low-intensity. NMDA receptor activation is required for INDUCTION of LTP.

Question 16

What are synaptic spines? How are they involved with learning?

Answer 16

Dendritic spines are the primary sites of contact between excitatory synapses and target cell. With learning new spines may form or be strengthened.

Question 17

How is LTP input specific?

Answer 17

LTP is input specific: LTP induced by activation of one synapse is not observed in other/inactive synapses that contact the same neuron. It is restricted to activated synapses, not all synapses on a neuron. In a memory model, this property allows selective storage of information at synapses

Question 18

How does LTP demonstrate associativity?

Answer 18

LTP demonstrates associativity: If weak stimulation of a pathway occurs when a neighboring pathway is strongly activated, then both synaptic pathways will undergo LTP. This is considered a cellular analog of associative or classical conditioning

Question 19

“The NMDA receptor-channel acts as a coincidence detector,” what does this mean? What is the co-agonist of NMDA receptors?

Answer 19

It requires ligand binding (e.g., glutamate or the pharmacological agent NMDA) + sufficient membrane depolarization to relieve the voltage-dependent blockade of its associated ion channel by Mg2+. Only then does the channel open and allow Ca2+ to enter the target neuron and activate downstream calcium-dependent processes important for synapse strengthening. the co-agonist glycine is also required for activation of NMDA receptors.

Question 20

Induction is achieved through what receptor type?

Answer 20

NMDA - TID

Question 21

How is expression or maintenance of LTP achieved?

Answer 21

By AMPA receptor expression in the postsynaptic membrane.

Question 22

How are metabotropic glutamate receptors thought to contribute to LTP?

Answer 22

Metabotropic glutamate receptor activation is thought to contribute because it promotes release of intracellular Ca2+ stores via IP3 as well as increases in PKC that enhances NMDA currents

Question 23

Does LTP involve protein kinases? Describe the role of Ca+:

Answer 23

The increases in intracellular Ca2+ activate a number of protein kinases via phosphorylation which enhance synaptic transmission: the production of substances that diffuse across the synapse and cause enhanced release of glutamate when there has been terminal depolarization. increase AMPA receptor currents by insertion of additional AMPA receptors. increase NMDA currents

Question 24

What happens to LTP if you shut down the ability to create proteins?

Answer 24

long-term LTP in hippocampus requires gene transcription and protein translation, including proteins associated with synaptic growth. Thus it would result in no LTP or loss of LTP if you did that.

Question 25

What is Long Term Depression (LTD)?

Answer 25

It is a long-lasting decrease in synaptic strength that provides an attractive neural mechanism for certain forms of learning and memory. It is observed at synapses throughout the brain.

Question 26

When can LTD be observed at Shaffer collateral-CA1 synapses?

Answer 26

In hippocampal area CA1, it is brought about by low-frequency (~1 Hz) stimulation for 10-15 minutes.

Question 27

Does LTD activate kinases? What happens?

Answer 27

No, like LTP, LTD shows input specificity and NMDAR-dependence, but the Ca signal differs. Small and slow rises in Ca lead to activation of phophatases, not kinases.

Question 28

How are AMPA receptors associated with LTD?

Answer 28

LTD is associated with internalization of AMPA receptors, not insertion of them into the postsynaptic membrane. This leads to a decrease in synaptic strength. LTD can erase LTP and vice versa, suggesting a common synaptic site of action.

Question 29

Summarize the mechanisms underlying LTD:

Answer 29

A low amplitude rise in calcium concentration in the postsynaptic CA1 neuron activates postsynaptic protein phosphatases, which cause internalization of postsynaptic AMPA receptors, thereby decreasing the sensitivity to glutamate release from the Schaffer collateral terminals

Question 30

TID TID TID

Answer 30

TID