Neuro Box 8

To remember this type of information, we must encode a form of mental conjunction, a unique memory trace that ——

records what, when, and where an event occurred

Research has shown that this ability depends on a portion of the forebrain, the hippocampus:

a seahorse shaped structure that lies under the cortical surface and is richly inter-connected with it

Insights regarding hippocampal function first emerged from work with a patient, known during his lifetime as ———. He underwent bilateral removal of the hippocampus and surrounding tissue → led to a devastating memory impairment that was studied by Brenda Milner

H.M

Insights regarding hippocampal function first emerged from work with a patient, known during his lifetime as H.M. He underwent ————-

bilateral removal of the hippocampus and surrounding tissue

Insights regarding hippocampal function first emerged from work with a patient, known during his lifetime as H.M. He underwent bilateral removal of the hippocampus and surrounding tissue → led to a devastating memory impairment that was studied by Brenda Milner

She found that his impairment had remarkable ——-.

specificity

Insights regarding hippocampal function first emerged from work with a patient, known during his lifetime as H.M. He underwent bilateral removal of the hippocampus and surrounding tissue → led to a devastating memory impairment that was studied by Brenda Milner

She found that his impairment had remarkable specificity.

• He could recognize objects and understand the meaning of words (———).

semantic memory

Insights regarding hippocampal function first emerged from work with a patient, known during his lifetime as H.M. He underwent bilateral removal of the hippocampus and surrounding tissue → led to a devastating memory impairment that was studied by Brenda Milner

She found that his impairment had remarkable specificity.

• He could recognize objects and understand the meaning of words (semantic memory).

• He could also recall events that happened years ago (———) and temporarily remember new information (———-), such as a phone number.

(long-term memory) ; (short-term memory)

Insights regarding hippocampal function first emerged from work with a patient, known during his lifetime as H.M. He underwent bilateral removal of the hippocampus and surrounding tissue → led to a devastating memory impairment that was studied by Brenda Milner

She found that his impairment had remarkable specificity.

• He could recognize objects and understand the meaning of words (semantic memory).

• He could also recall events that happened years ago (long-term memory) and temporarily remember new information (short-term memory), such as a phone number.

  • However, he lost the capacity to transfer new information into long-term memory and later consciously recall it. He lost the ability to —

encode distinct episodes within his life

Insights regarding hippocampal function first emerged from work with a patient, known during his lifetime as H.M. He underwent bilateral removal of the hippocampus and surrounding tissue → led to a devastating memory impairment that was studied by Brenda Milner

She found that his impairment had remarkable specificity.

• He could recognize objects and understand the meaning of words (semantic memory).

• He could also recall events that happened years ago (long-term memory) and temporarily remember new information (short-term memory), such as a phone number.

  • However, he lost the capacity to transfer new information into long-term memory and later consciously recall it. He lost the ability to encode distinct episodes within his life, a deficit in —— that is also seen with the dementia of Alzheimer’s disease, which causes a disruption in hippocampal function.

episodic memory

The role of the hippocampus in learning and memory has been extensively studied using ——-

laboratory animals and experimentally-induced lesions

Because the hippocampus is richly inter-connected with the over-lying cortex, it receives input related to multiple dimensions, including:

• color

• sound

• time

• location

Because the hippocampus is richly inter-connected with the over-lying cortex, it receives input related to multiple dimensions, including color, sound, time, and location.

By binding together the constellation of cues that define a particular moment in time, it can provide ——-

a snapshot that represents unique stimulus configurations.

Because the hippocampus is richly inter-connected with the over-lying cortex, it receives input related to multiple dimensions, including color, sound, time, and location.

By binding together the constellation of cues that define a particular moment in time, it can provide a snapshot that represents unique stimulus configurations.

What distinguishes the hippocampus is that accomplishes this feat —-

in a rapid manner, incidentally in the absence of explicit reinforcement

a rat will encode the unique configuration of cues that define a new environment (context).

• This is readily shown using a Pavlovian task in which a rat is given a mild shock (the US) within a novel context.

• If the shock is given 2-3 min after the rat is placed in the environment, it will exhibit —— when it is re-exposed to the context the next day.

conditioned fear (freezing)

a rat will encode the unique configuration of cues that define a new environment (context).

• This is readily shown using a Pavlovian task in which a rat is given a mild shock (the US) within a novel context.

• If the shock is given 2-3 min after the rat is placed in the environment, it will exhibit conditioned fear (freezing) when it is re-exposed to the context the next day.

  • If, however, shock is given immediately after the rat is placed in the chamber, before it can presumably form a conjunctive representation of the context, it ———

fails to associate the context with shock

a rat will encode the unique configuration of cues that define a new environment (context).

• This is readily shown using a Pavlovian task in which a rat is given a mild shock (the US) within a novel context.

• If the shock is given 2-3 min after the rat is placed in the environment, it will exhibit conditioned fear (freezing) when it is re-exposed to the context the next day.

  • If, however, shock is given immediately after the rat is placed in the chamber, before it can presumably form a conjunctive representation of the context, it fails to associate the context with shock.

    • This ——- can be eliminated by simply exposing the rats to the context for 2-3 min the day before.

immediate shock deficit

a rat will encode the unique configuration of cues that define a new environment (context).

• This is readily shown using a Pavlovian task in which a rat is given a mild shock (the US) within a novel context.

• If the shock is given 2-3 min after the rat is placed in the environment, it will exhibit conditioned fear (freezing) when it is re-exposed to the context the next day.

  • If, however, shock is given immediately after the rat is placed in the chamber, before it can presumably form a conjunctive representation of the context, it fails to associate the context with shock.

    • This immediate shock deficit can be eliminated by simply exposing the rats to the context for 2-3 min the day before.

It appears that rats must first ———— before ———-

(first) encode the configuration of cues that define a context

(before) the context can be associated with shock.

Lesioning the hippocampus eliminates the capacity of—

(of) context conditioning

Lesioning the hippocampus eliminates the capacity of ——

(capacity of) context conditioning

Lesioning the hippocampus eliminates the capacity of context conditioning Importantly, it does so without affecting—-

the capacity to learn that a discrete cue (e.g., a tone) predicts shock.

fear conditioning depends upon the——

(upon the) basolateral region of the amygdala

fear conditioning depends upon the basolateral region of the amygdala, where —-

he cue (the CS) and shock (the US) are joined.

a —- cue provides a direct input to the amygdala

simple

context conditioning depends on the ———- from the hippocampus.

derivation of a conjunctive representation and output

If the hippocampus is lesioned, the rat will notice that an object has been changed (——) but not whether its location has been changed (——-).

(object memory); (spatial memory)

esearchers have worked to uncover the neurobiological mechanisms that allow it to encode new information. This work has revealed a cellular system for —-

altering synaptic strength that is used throughout the nervous system

esearchers have worked to uncover the neurobiological mechanisms that allow it to encode new information. This work has revealed a cellular system for altering synaptic strength that is used throughout the nervous system.

Electrophysiological studies showed that a strong neural input can—-

strengthen the synaptic connection between two cells

Electrophysiological studies:

lowered an electrode into a bundle of neurons in the hippocampus known as the perforant path and applied an electrical current . The cells that form the perforant path synapse on hippocampal neurons called mossy fibers. By recording neural activity through electrodes placed near the mossy fiber cell bodies, Bliss and Lomo obtained a measure of synaptic strength

perforant path:

the bundle of neurons in the hippocampus

mossy fibers:

The cells that form the perforant path synapse on hippocampal neurons

applying a moderate electrical stimulus to the perforant path elicited ——- in the mossy fibers and this response changed little over time.

moderate neural activity i

applying a moderate electrical stimulus to the perforant path elicited moderate neural activity in the mossy fibers and this response changed little over time.

But if a strong input was provided, one that caused a very strong response (———-) in the mossy fibers, subsequent inputs produced a much larger response.

(depolarization) i

applying a moderate electrical stimulus to the perforant path elicited moderate neural activity in the mossy fibers and this response changed little over time.

But if a strong input was provided, one that caused a very strong response (depolarization) in the mossy fibers, subsequent inputs produced a much larger response.

This phenomenon is called——

(called) long-term potentiation (LTP).

In the absence of LTD, input to the hippocampus could —-

saturate plasticity, which would prevent further learning.

LTP has a number of properties that suggest it plays a role in learning and memory:

• its enduring nature

• cooperativity

• associativity

A strong input could increase the strength of a chemical synapse and induce LTP by enhancing ——— or ———

either the amount of transmitter released (or) the responsiveness of the postsynaptic cell

LTP is largely due to ——

increased responsiveness of the postsynaptic cell.

The presynaptic cell releases a neurotransmitter (glutamate) that can engage two types of receptors (——- & ——-) on the postsynaptic cell

(AMPA & NMDA)

Engaging the AMPA receptor: 

allows Na+ to enter the cell and initiates the chemical processes that produce an action potential

The NMDA receptor operates in a different manner and regulates ——

the flow of Ca++ into the cell

At rest, the NMDA channel is blocked by the ion

magnesium (Mg++).

At rest, the NMDA channel is blocked by the ion magnesium (Mg++).

• For the NMDA receptor to work, this Mg++ must be

displaced, (which requires a strong depolarization of the postsynaptic cell)

At rest, the NMDA channel is blocked by the ion magnesium (Mg++).

• For the NMDA receptor to work, this Mg++ must be displaced, which requires a strong depolarization of the postsynaptic cell.

  • This can be produced by —-

strongly engaging the AMPA receptors at the same synapse or from a depolarization provided at another synapse on the same cell

At rest, the NMDA channel is blocked by the ion magnesium (Mg++).

• For the NMDA receptor to work, this Mg++ must be displaced, which requires a strong depolarization of the postsynaptic cell.

• This can be produced by strongly engaging the AMPA receptors at the same synapse or from a depolarization provided at another synapse on the same cell.

  • In either case, when the Mg++ block is removed, the release of —- engages ——

glutamate from the presynaptic cell engages the NMDA receptor and allows Ca++ to flow into the cell.

At rest, the NMDA channel is blocked by the ion magnesium (Mg++).

• For the NMDA receptor to work, this Mg++ must be displaced, which requires a strong depolarization of the postsynaptic cell.

• This can be produced by strongly engaging the AMPA receptors at the same synapse or from a depolarization provided at another synapse on the same cell.

  • In either case, when the Mg++ block is removed, the release of glutamate from the presynaptic cell engages the NMDA receptor and allows Ca++ to flow into the cell.

    • This initiates biochemical processes within the cell that enhance—-

• AMPA receptor function.

biochemical processes within the cell that enhance AMPA receptor function. This is accomplished in two ways:

• One is by chemically altering (phosphorylating) the receptor, a modification that enhances the flow of positively charged ions into the cell.

• The other is by initiating the movement (trafficking) of additional AMPA receptors into the active region of the postsynaptic membrane

biochemical processes within the cell that enhance AMPA receptor function. This is accomplished in two ways:

• One is by

chemically altering (phosphorylating) the receptor, a modification that enhances the flow of positively charged ions into the cell.

biochemical processes within the cell that enhance AMPA receptor function. This is accomplished in two ways:

• One is by chemically altering (phosphorylating) the receptor, a modification that enhances the flow of positively charged ions into the cell.

  • The other is by initiating —-

the movement (trafficking) of additional AMPA receptors into the active region of the postsynaptic membrane

trafficking can even —- a synapse that was silent because there were no AMPA receptors in the active zone.

turn on (awaken)

trafficking can even turn on (awaken) a synapse that was silent because there were no AMPA receptors in the active zone.

• LTD is mediated by these same chemical processes, but —

• n the opposite direction.

the NMDA receptor acts as a kind of coincidence detector:

For it to function, two conditions must be met—there must be both presynaptic release of glutamate and a strong depolarization.

hat the NMDA receptor is only needed for the ——- of LTP (or LTD). Once the synapse has been changed, synaptic communication depends on the AMPA receptor alone.

induction

hat the NMDA receptor is only needed for the induction of LTP (or LTD). Once the synapse has been changed, synaptic communication depends on the AMPA receptor alone.

As a result, drug antagonists that disrupt NMDA function (———) prevent the induction of LTP but not its maintenance.

(e.g., MK-801 or APV)

To explore whether hippocampal LTP plays a functional role within the living organism (———’), researchers have examined whether treatment with a NMDA antagonist affects learning and memory in tasks that depend upon hippocampal function

(in vivo, Latin from ‘within the living’),

disrupting NMDA receptor function undermines ——- but not ——

fear conditioning to a context (but not) an embedded (discrete cue).

the NMDA receptor antagonist MK- 801 disrupts —-learning within the Morris water maze. Importantly, in both cases, local infusion of the drug disrupts learning, but not memory retrieval

spatial

the NMDA receptor also contributes to learning and memory in other neural systems, including the:

• cerebellum

• amygdala

• nucleus accumbens

• spinal cord

Overturning the long-standing view that brain neurons do not regenerate, Gould and her colleagues have found evidence for the birth of new neurons (———) within the hippocampus.

neurogenesis

Exercise and environmental enrichment promote this process, whereas ——inhibits neurogenesis

stress