Memory And Amnesias

Question 1

What are the types of memory?

Answer 1

Declarative (Explicit)

1. Facts- What is the capital of Georgia?
2. Events- Remember the dance?

Procedural (Implicit) Nondeclatrative memory

1. Skills/Habits- riding a bike
2. Conditionin

Question 2

What are the types of procedural memory?

Answer 2

Priming

Skills/habits

Conditioning

Question 3

What are the stages of memory?

Answer 3

Encoding—> retrieval —> consolidation

Question 4

How can we examine for a deficient in initial encoding?

Answer 4

Explanation: If a patient cannot learn new words even after repeated trials and mental rehearsal, this suggests a deficit in initial encoding. The patient will not be able to recall these words after a short or long delay, nor will this patient be able to retrieve them so technically, a deficit in encoding will result in deficits in all the other memory stages as well but the initial problem is in the encoding stage. If a patient can encode new words but rapidly forgets them, then this is a problem in the short-term memory stage.

This is a pattern typically seen in Alzheimer’s Disease. If there is a deficit in short-term memory, there will also be a deficit in long-term memory and retrieval because the words were never successfully consolidated. If a patient initially encodes words and recalls them after a short delay but forgets them after a long delay, then this is a problem in long-term memory.

In this case, retrieval would also be impaired. If the patient cannot recall words off the top of his head but can recognize them if they are listed amongst distractors, then this suggests a problem with retrieving the words from memory. The patient may be able to consolidate new words but just cannot retrieve them from memory storage without help

Question 5

What are the types of amnesias?

Answer 5

Retrograde Amnesia

Anterograde Amnesia

Question 6

What are the forms 9f amnesia?

Answer 6

Infantile amnesia: early childhood events cannot be recalled

Transient global amnesia: occurs typically in older men, recent events, and information can only remembered for a few minutes. Normally all other functions are not impaired. Possible causes: TIA, basilar artery migraine, physical or psychic stress.

Dissociative amnesia: psychological reaction (witness of a severe accident or crime)

Question 7

What are the diagnostic criteria of amnesia?

Answer 7

Diagnostic Criteria

►Memory loss for autobiographical information, which doesn’t occur due to another disorder.
►Memory loss can be:

•Localized: Total loss of personal memory during a
circumscribed period

• Selective: Some (but limited) recall of personal memories during a circumscribed period of time
• Generalized: Loss of personal memory of entire life up to and including event

Question 8

What is diencephalic amnesia?

Answer 8

Wernicke-Korsakoff amnesia (diencephalic amnesia): caused by thiamin deficiency in patients with alcohol abuse; symptoms include confusion, confabulation, and severe memory impairment

Question 9

Contrast diencephalic amnesia with bilateral Mesial temporal amnesia (H.M.)

Answer 9

Diencephalic (N.A., WK)
Intact IQ
Intact procedural learning Anterograde memory deficit Retrograde memory deficit Impaired encoding
Intact consolidation
Poor insight, confabulation

Bilateral Mesial Temporal (H.M.)
Intact IQ
Intact procedural learning 
Anterograde memory deficit 
Retrograde memory deficit Impaired encoding
Impaired consolidation Intact insight

Question 10

What is an Engram?

Answer 10

Neurons that fire
together wire
together

The connections between the neurons are strengthened through repeated co-firing

A hypothetical change in neural tissue that is believed to account for the persistence of memory

Synaptic Plasticity
Short term: Transient changes in synaptic function
(perhaps mediated through altered metabolism)

Long term: More permanent alteration of cellular function (perhaps change of protein expression and/or change of cellular structure)

Question 11

Whaat are the locations of engrams in the brain?

Answer 11

Memory engrams are located in distributed parts of the neocortex and most of these regions comprise association areas receiving sensory information from primary sensory areas such primary visual cortex, auditory cortex and somatosensory cortex.

Association areas send new sensory information to the medial temporal lobes for processing in the hippocampal formation which then relies on thalamo- hippocampal-cortical loops to keep the neuronal assemblies co-active (i.e., rehearsal) until they are “bound” into a more permanent memory trace (i.e., consolidation).

The engram exists as assemblies of neurons in neocortex with synapses showing significant plastic alteration in synaptic efficiency. Some areas are concerned with information about facts, events, language and places whereas other areas store information about the emotional content of our memories.

Prefrontal neocortical areas support attention and working memory during initial memory formation and also information about the context/source of the memory which helps to relate memories to the time and place in which the stored information was received

Question 12

What is the location of the hippocampus?

Answer 12

Question 13

Describe the hippocampal trisynaptic circuit

Answer 13

Question 14

Contrast the extra-hippocampal circuitry (papez circuit) and intra-hepatic

Answer 14

Question 15

What is the result of seed tracking the complete Pap3z circuit?

Answer 15

Question 16

Illustrate seed points for paper circuit in Sagittarius and coronal view

Answer 16

Question 17

Summarize standard consolidation theory

Answer 17

Summary:
• The hippocampus is the conductor of the memory engram symphony

• The hippocampus and surrounding regions come online to bind sensory traces from various cortical regions (via entorhinal) into a cohesive memory engram.
• These symphonies are rehearsed often enough (via diencephalic system) until the band can play on its own, without the hippocampus.
• These hippocampal independent symphonies (i.e., long term memories) are robust to hippocampal damage (as in HM) but will not form in the absence of sober (i.e., functionally intact) conductor

Question 18

Summarize the multiple trace model of functional anatomy of memory

Answer 18

One more word on hippocampal “independent” memories:

• The standard consolidation model of memory suggests that memories eventually become hippocampal independent.
• Multiple trace models of memory suggest that memory recall always activates the hippocampus to some extent.
• Memory retrieval brings an engram “online” to incorporate new information and form “multiple traces”
• Reconsolidation: Reactivation of memory traces renders them labile/malleable via involvement of hippocampal system

Question 19

What is the tri-synaptic hippocampal pathway?

Answer 19

The hippocampus is a crucial structure within the hippocampal formation consisting of dentate gyrus, hippocampus and subiculum. This folded cortical structure is a three-layered region of cortex in the medial temporal lobes.

Neurons in the entorhinal cortex relay excitatory signals to cells in the dentate gyrus which in turn excite CA3 cells in the hippocampus. The CA3 cells have collateral axons that make excitatory synapses with CA1 neurons in the hippocampus.

The CA1 neurons pass on the excitatory message to cells in the subiculum which, in turn, relay signals back to the entorhinal cortex. Impulses passing through this loop induce synaptic plasticity at synapses on cells of the dentate gyrus, hippocampus and the subiculum.

Question 20

Explain long term potentiation in hippocampus

Answer 20

Long-Term Potentiation in Hippocampus is Input Specific

Response of a rat CA1 neuron to 2 different inputs:

Input 1: high-frequency tetanus (100 Hz/min for 20 min) → potentiated response Input 2: no change after moderate frequency input

Question 21

Long term potentiation relies ligand and voltage gated channels

Answer 21

1. glutamate released from presynaptic terminals
2. glutamate binds with both AMPA and NMDA receptors on post-synaptic membrane
3. binding opens AMPA channels for Na+ entry
4. EPSPs summed to elicit depolarization
5. Voltage-gated opening NMDA receptor channels by removal of Mg2+
6. Ca2+ entry through NMDA channel activates 2nd messenger pathways
7. 2nd messenger pathways activate protein kinases, mRNA modeling of new AMPA receptors
8. 2nd messenger pathways trigger release of retrograde messengers
9. Retrograde messengers stimulate lasting increase in pre-synaptic glutamate release

Question 22

How can synaptic strength/ efficiency be increased?

Answer 22

An increase in AMPA channel conductance (early effect)

• An increase in the number of AMPA receptors (early effect)
• An increase in the number of synapses involving formation of new dendritic spines and increased synaptic boutons (late effect)

Question 23

Explain long term potentiation in in the tri-synaptic hippocampal pathway

Answer 23

Long-term potentiation (LTP) in the tri-synaptic hippocampal pathway

When CA1 neurons are excited by a high frequency (about 100/ s) train of impulses along the Schaffer collateral axons of a CA3 neuron the excitatory synapse undergoes a large long-lasting increase in synaptic efficiency called long term potentiation (LTP). The synapses showing this potentiation are glutamatergic synapses on dendritic spines in the CA1 neuron.

Postsynaptic Changes in CA1 Neurons: During the onset of LTP the early change occurring in the CA1 neuron is an increase in the sensitivity to the excitatory transmitter glutamate owing to insertion of new AMPA receptors for glutamate in the membrane of the dendritic spines. A later change that makes the CA1 neuron more responsive to its excitatory input from the CA3 neuron is an increase in the number of synapses between the CA3 and the CA1 neurons, i.e. formation of new dendritic spines and associated synaptic bouton

Question 24

How does NMDA receptor cause long term potentiation in the tri-synaptic hippocampal pathway?

Answer 24

NMDA Receptor Activation causes LTP: A single presynaptic impulse releases glutamate into the cleft where it binds to AMPA and NMDA receptors in the postsynaptic membrane; The AMPA receptor cation channels open and the ensuing entry of Na+ ions produce an EPSP. But each NMDA receptor channel remains blocked by a Mg2+ ion within the channel. A train of presynaptic impulses cause a prolonged and enlarged depolarization of the postsynaptic cell by temporal summation. The enhanced depolarization drives Mg2+ ions out of the channels and this unblocking allows Ca2+ ions to enter the postsynaptic cell.
Thus, tetanic stimulation causes a rise in intracellular [Ca 2+] and this leads to activation of two protein kinases — protein kinase C and calcium-calmodulin- dependent protein kinase II (also called CAMKll). Activation of these enzymes alters the phosphorylation of key membrane proteins including AMPA receptors and there is evidence that these support LTP.

There are three elements in the development of LTP at these synapses all of which have origins in the postsynaptic cells.

These elements are:

• an increase in the AMPA channel conductance (an early effect)
• an increase in the number of AMPA receptors (an early effect)
• an increase in the number of synapses (a late effect) involving the formation of new dendritic spines and an induced increase in the number of synaptic boutons

Question 25

How can long rwrm depression in the hippocampus be input sp3cifuc ?

Answer 25

Response of a rat CA1 neuron to 2 different inputs:
Input 1: low-frequency tetanus (1 Hz/min for 20 min) → depressed response

Input 2: no change after moderate frequency input

Question 26

How can we decrease synaptic strength/efficiency?

Answer 26

• A decrease in AMPA channel conductance (early effect)
  • A decrease in the number of AMPA receptors (early effect)
  • A decrease in synaptic density (late effect)

Question 27

Explain the consequences of long term depression(LTD) in in th3 tri-synaptic hippocampal pathway

Answer 27

When a CA1 neuron is excited by an impulse train at low frequency (about 1 / s) train of impulses passing along the Schaffer collateral axons of a CA3 neuron the excitatory synapse undergoes a large persistent fall in synaptic efficiency term depression (LTD). Thus, the same synapses that show LTP when stimulated intensively can also show LTD when stimulated weakly by CA3 neurons.

The activation of NMDA receptors is a prerequisite for both LTD and LTP. The crucial difference is the different rises in intracellular [Ca2+ ] that are produced by intense and weak stimulation of the axons of the CA3 neurons.

The role of [CA 2+ ] for LTP and LTD: High frequency stimulation (HFS) induces a rise in the intracellular [Ca2*] in the CA1 neuron that exceeds 5 pM (picometers). This rise is sufficient to activate two kinases (see above) that alter the phosphorylation of key proteins leading to LTP. On the other hand, low frequency stimulation (LFS) induces a relatively small rise in the intracellular [Ca2+ ] of about 1 μM (micrometer, micron) or less. At those low levels different enzymes — protein phosphatases — are activated. These enzymes cause dephosphorylation of proteins including AMPA receptors.

Evidently the dephosphorylations steps induce internalization of AMPA receptors. This reduction causes a persistent fall in the sensitivity of the CA1 neuron to glutamate, thus depressing the size of the EPSPs and endowing the synapse with LTD.

Question 28

Contrast LTP and LTD in Ca2+ concentration

Answer 28

HF stimulation causes LTP through large elevation of [Ca2+]

LF stimulation causes LTD through smaller elevation of [Ca2+]

Question 29

Contrast LTP and LTD for NMDA receptor activation

Answer 29

LTP versus LTD: NMDA receptor activation and bidirectional synaptic plasticity

Postsynaptic neuron strongly depolarized: large amounts of [Ca2+] enter postsynaptic neuron → activation of protein kinases.

Postsynaptic neuron weakly depolarized: small amounts of [Ca2+] enter postsynaptic neuron → activation of protein phosphatases.

Phosphatases cause dephosphorylation and internalization of AMPA receptors.