Week 1 - Cellular mechanisms of learning and memory

Question 1

declarative memory and examples

Answer 1

storage and retrieval of material that is available to consciousness

• daily episodes
• words and their meanings
• history
• can bring them up and talk about them if need be

Question 2

nondeclarative (procedural) memory and examples

Answer 2

not available to consciousness, and involves skills or associations that are acquired and retrieved at an unconscious level

• motor skills
• priming cues
• puzzle solving skills

Question 3

what did H.M have removed and why? what were the effects?

Answer 3

suffered from intractable epilepsy (drugs didn’t help, seizures incapacitated him) so underwent bilateral medial temporal lobe resection causing destruction of uncus, amygdala, periamygdaloid cortex, and anterior 2/3 of hippocampus
-epilepsy was relieved, with normal IQ, short-term working memory, and intact retrograde memory before surgery, but severely compromised anterograde memory

Question 4

what kind of memory could H.M. still form?

Answer 4

procedural/reflexive memories (nondeclarative motor skill memory)
-star tracing task showed skill improvement, despite never consciously remembering doing the test

Question 5

what were R.B.’s symptoms and what did autopsy reveal?

Answer 5

more modest memory impairment than H.M.’s due to cardiac arrest anoxia
-autopsy revealed specific bilateral brain damage to area CA1 of hippocampus

Question 6

what does spatial learning and memory in rodents depend on? what test proved this?

Answer 6

hippocampus
-rats placed in a swimming pool, and those with hippocampal lesions couldn’t find the hidden platform even after 10 trials, while control rats could

Question 7

what brain areas are associated with declarative memory disorders?

Answer 7

fornix and mammillary body (ending of fornix)
thalamus
basal forebrain
prefrontal cortex
amygdala
rhinal cortex
hippocampus

Question 8

projections of declarative memory storage sites

Answer 8

widespread projections from association neocortex converge on hippocampal region
-output of hippocampus is ultimately directed back to these same neocortical areas

Question 9

how is memory categorized in terms of time over which it is effective?

Answer 9

immediate memory - fractions of seconds
working memory - seconds to minutes
long-term memory - days to years

Question 10

what is working memory?

Answer 10

ability to hold and manipulate information for seconds to minutes while used to achieve particular goal (also short term memory)
-limited in duration and capacity

Question 11

does immediate and short term memory information enter long-term memory?

Answer 11

some, but most is forgotten

Question 12

what are the short term and long term memory storage for declarative information?

Answer 12

short term: hippocampus and related structures
long term: variety of cortical sites (Wernicke’s area for meaning of words, temporal cortex for memories of objects/faces)

you need the hippocampus to make memories, but they are stored elsewhere

Question 13

what are the short term and long term memory storage for nondeclarative information?

Answer 13

short term: sites unknown, but presumably widespread

long term: cerebellum, basal ganglia, premotor cortex, other sites related to motor behavior

Question 14

what is the ENGRAM?

Answer 14

physical embodiment of long-term memory
-depends on long-term changes in efficacy of synaptic transmission (growth and/or reordering of relevant synaptic connections)

Question 15

what is consolidation?

Answer 15

transfer of declarative memory from hippocampus to cortical structures for long-term storage

Question 16

what is long-term potentiation?

Answer 16

long-lasting increase in synaptic strength that forms an attractive neural mechanism for certain forms of learning and memory in declarative memory

• observed in synapses throughout brain, especially at Shaffer collateral-CA1 synapses in hippocampus
• consequence of enhanced synaptic transmission
• -more cells may fire in response to same low-frequency, low-intensity stimulus used prior to brief tetanus

Question 17

what are Schaffer collaterals?

Answer 17

axons from pyramidal CA3 neurons in the hippocampus that are sent to pyramidal CA1 neurons
-exhibit LTP

Question 18

what are the 3 major pathways that form intrinsic trisynaptic circuitry?

Answer 18

1. perforant path (from entorhinal cortex) to dentate granule cells
2. dentate granule cell projections to area CA3 pyramidal cells
3. CA3 pyramidal cell projections to CA1 pyramidal cells
   they all exhibit LTP

Question 19

what is LTP protocol?

Answer 19

1. baseline recording established by providing low-frequency, low-intensity stimulus (only AMPA receptors activated)
2. pathway 1 gets brief high-frequency, high-intensity stimulus (NMDA activated by tetanus) while pathway 2 only low/low
3. LTP observed only in 1 (reflected by strengthening of EPSP after returning to low-frequency, low intensity stimulus initially used to establish baseline)

Question 20

what is required for induction of LTP?

Answer 20

NMDA receptor activation

Question 21

what are dendritic spines? what happens there?

Answer 21

the primary site of contact between excitatory synapses and target cells

• axodendrites synapse on it
• spines may change shape or appear elsewhere if an LTP occurs

Question 22

what is specificity in terms of LTP? what does this mean for the memory model?

Answer 22

LTP is input specific

• LTP induced by activation of one synapse is not observed in other inactive synapses that contact the same neuron
• restricted to activated synapses, not all synapses on a neuron
• in memory model, this property allows selective storage of info at synapses (so only LTP in one place)

Question 23

what is associativity in terms of LTP?

Answer 23

LTP demonstrates associativity

• if weak stimulation of a pathway occurs when a neighboring pathway is strongly activated, then both pathways undergo LTP
• considered a cellular analog of associative or classical conditioning

Question 24

how is the NMDA receptor channel a coincidence detector?

Answer 24

requires ligand binding + sufficient membrane depolarization to relieve voltage-dependent blockade of associated ion channel by Mg++ + co-agonist glycine
-only then does the channel open and allow Ca++ to enter target neuron and activate downstream Ca-dependent processes important for synapse strengthening

Question 25

what does the expression/maintenance of LTP involve?

Answer 25

increased AMPA receptor expression in postsynaptic membrane (due to effects of calmodulin kinase II and PKC causing substrate phosphorylation)
-may also need increase in glutamate release from presynaptic terminals

Question 26

how are AMPA receptor currents increased?

Answer 26

PKA and CaMKII (phosphorylated) insert additional AMPA receptors into membrane

Question 27

what increases NMDA currents?

Answer 27

PKC and PTK

Question 28

what does anisomycin do?

Answer 28

protein synthesis inhibitor

-causes LTP to decay within a few hours of tetanus that induces LTP

Question 29

how does long-term LTP in hippocampus occur?

Answer 29

transcription and translation, including PRO associated with synaptic growth

• kinases diffuse to CA1 cell nuclei, incluencing genes that trigger long-lasting post-synaptic modifications
• in presynaptic terminals, kinases activated that diffuse to CA3 nuclei and influence genes that cause presynaptic structural modifications

Question 30

what does LTP induction do to synapses on dendritic shafts and spines?

Answer 30

it increases the number of synapses on dendritic shafts and in stubby spine synapses

Question 31

how do the number of presynaptic terminals increase?

Answer 31

they increase by axon terminal sprouting

Question 32

what is long term depression? where is it observed?

Answer 32

LTD - long-lasting decrease in synaptic strength that provides an attractive neural mechanism for certain forms of learning and memory
-it’s observed at synapses throughout brain, especially at Shaffer collateral-CA1 synapses when stimulated at a low rate for long periods

Question 33

why does LTD exist?

Answer 33

if synapses continued to increase in synaptic efficacy as a result of LTP, eventually would reach level of maximum efficacy, making it hard to encode new information
-LTD can erase LTP and vice-versa, suggesting common synaptic site of action

Question 34

how does LTD occur in hippocampal area CA1?

Answer 34

it is brought about by low frequency stimulation (1 Hz) for 10-15 minutes

• activates AMPA, NMDA, and mGlu receptors, which causes increased intracellular Ca, which activates PRO phosphatases
• activation of Ca-dependent PRO phosphatases leads to internalization of AMPA receptors, which reduces synaptic efficacy