(OBJ) Describe the brain lesion imposed on patient HM and the memory deficit that ensued.
LESION - bilateral removal of hippocampus, amygdala, and overlying temporal cortex in 1953
DEFICIT:
–Memories before 1949: fine
–Memories between 1949-1952: partially degraded
–No long-term memories post-surgery (only retention for 30-40 seconds
–Motor/procedural memory intact, but declarative memory/names not
(OBJ) Describe the difference between declarative and nondeclarative memory and the major brain areas associated with declarative memory.
DECLARATIVE (explicit): “that”
- -True/false
- -Involves modeling of the external world
- -Storage of facts and episodes
- -Conscious
- -Highly flexible, many components
- -Further categorized into episodic (memory of personal experience) and semantic (words/concepts
NONDECLARATIVE (implicit): “how”
- -Procedural, not propositional
- -Changes in skilled behaviors
- -Not conscious (e.g. motor learning
Four basic phases of explicit memory (knowing definitions not critical, but have an idea of the concepts)
Encoding: processes by which new information is attended to and linked to existing information
Storage: both the mechanisms and the actual parts of the brain for memory retention
Consolidation: processes that endow temporary memories with permanence
Retrieval: recall
What structures make up the hippocampal formation? (4)
Hippocampal formation = hippocampus, dentate gyrus, subiculum, entorhinal cortex
What is working memory? Where is it stored? What two neurotransmitters can modulate its efficiency?
WORKING MEMORY
- -Two components: visual/spatial information & verbal information
- -Temporary, limited storage space
- -Stored in prefrontal cortex
- -Modulated by ACh and D1 dopamine receptors (must be at correct level)
(OBJ) Describe the role of the hippocampus in learning and memory.
Hippocampus required for all four stages of memory (encoding, storage, consolidation, and retrieval)
- -Not the ultimate site of storage, but does store memories initially, and retrieves memories from their storage places in neocortical regions
- -Neurons of hippocampus are very highly organized
(OBJ) Describe the phenomenon of long-term potentiation (LTP) and how it relates to memory. List three structural and three functional changes that contribute to LTP.
LTP: a long-lasting, activity-dependent increase in synaptic efficacy at an individual synapse (plasticity)
- -Functional changes: postsynaptic receptor number/channel function, presynaptic neurotransmitter release
- -Structural changes: # of postsynaptic spines, size of spine heads, spine stability
The hippocampus receives information from all of the senses, as well as the spatial relevance of that information from where?
The adjacent entorhinal cortex
What is Hebb’s neurophysiological postulate (the fundamental basis for LTP)?
When an axon of cell A is near enough to excite a cell B and repeatedly and persistently takes part in firing it, some growth or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased
–Following high level presynaptic activity, the size of the synaptic field potentials in postsynaptic neurons are larger than they were before, and remain this way for quite a while
Define induction, as it relates to LTP. What four things are required to induce LTP?
Induction: the biochemical processes that arise from the high level of activity
- Presynaptic: lots of activity, lots of glutamate
- Postsynaptic must be depolarized
- Glutamate must activate AMPA receptors (fast excitatory transmission) AND NMDA receptors
- Ca2+ must enter postsynaptic cell
Compare AMPA receptors and NMDA receptors.
AMPA receptors
–Mediate fast excitatory transmission
NMDA receptors
- -Key mediators of LTP
- -Permeable to Na and K
- -**HIGH Ca permeability
- -Erev > 0 mV
- -**Blocked by Mg at membrane potentials more negative than -30 mV - so doesn’t function at low potentials
(OBJ) Describe NMDA receptor and how it acts as a coincidence detector in the hippocampal circuitry.
NMDA receptor detects HIGH FREQUENCY ACTIVITY
- Rest/low activity: low glutamate released from presynaptic terminals -> AMPA receptors -> small amount of depolarization
- -NMDA receptor also binds glutamate, but doesn’t conduct current because channel is occluded by Mg2+ - High presynaptic activity: more glutamate released -> AMPA receptors -> greater depolarization in the postsynaptic spine
- -If that depolarization reaches ~ -40 mV, the depolarization repels the Mg2+ from the mouth of the NMDA receptor, allowing it to open and positive ions to flow into the cell. - Result = greater depolarization
- -More relief of Mg2+ block = more positive ion flux into the cell = more depolarization, etc. -> parallel increase in the activity of the presynaptic terminal (lots of glutamate release) and concomitant high level of depolarization in the postsynaptic spine. - In this way, the NMDA receptor acts as a coincidence detector and is the molecular signal for satisfying Hebb’s postulate.
In the context of LTP, define synapse-specificity and associativity. What synaptic structure promotes these two things?
Synapse-specificity: ONLY the synapse receiving high frequency stimulation and very near neighbors are potentiated
Associativity: neighboring synapses that are weakly stimulated may be potentiated by stimulation of that neighbor, especially if there is either repeated pairing of the two stimuli or if there is a strong emotional content to one of the stimuli
Neck (constriction point) acts as physical barrier to keep the signaling molecules in the synapse, so that they don’t leak out and affect nearby synapses
Describe four rapid changes that occur in dendritic spines in the development of LTP. ((OBJ) Describe the specializations present in dendritic spines and their relevance to generating specificity for LTP.)
- Insertion of new AMPA receptors from vesicles in the spine heads -> increased glutamate sensitivity
- -Calcium -> kinases/proteases (**CAMKII) -> insertion + receptor stability via phosphorylation - Phosphorylation of AMPA receptors -> increased single channel conductance -> increased sensitivity to glutamate
- Dynamic restructuring of the actin cytoskeleton -> enlargement/increased stability of active spines/new spines
- Increased release of glutamate from the PREsynaptic cell via retrograde messengers (NO & BDNF)
(OBJ) Describe the role of receptor insertion and retrieval in LTP and LTD (long-term depression).
(OBJ) Describe the role of calcium concentration in governing the expression of LTD vs. LTP.
LTD: dribble through NMDA receptor -> low levels of Ca -> activation of phosphatases -> internalization of receptors + dephosphorylation of AMPA receptors
(OBJ) Describe the effect of stress on LTP and learning. (but don’t remember all details, just overview)
Stress –> increased glucocorticoids –> enhanced glutamatergic transmission –> increased glutamate release/stimulation of AMPA receptors –> enhanced basal level of glutamatergic transmission –> resets LTP threshold UP and LTP threshold DOWN –> impaired LTP, enhanced LTD
—This all goes away if you have control over the stress
