10 - Hippocampus

strong epilepsis

—> Bilateral lobectomy (part of Hippocampus was removed)

• Memories established before lesion ⟹ NORMAL

• New short-term (up to a few minutes) memories ⟹ NORMAL

• Creation of new long-term explicit memories ⟹ IMPAIRED

• Development of new long-lasting implicit memory ⟹ NORMAL

medial temporal lobes:

• formation of semantic / episodic long-term memories

• working memory not rely on MTL

• lexical memory not rely on MTL

• spatial memory associated with hippocampus

Learning —> process, organism gets knowledge of world

Memory —> process, knowledge is encoded, stored, retrieved

(declarative memory)

recalled by conscious effort —> you are aware trying to remember sth

factual knowledge of people, places, things, events

e.g. try to remember wedding date

(non-declarative memory)

recalled unconsciously —> skills, habits and tasks that are performed automatically

e.g riding bicycle / driving car

• CA1 cell —> receives input from CA3 via Schaffer colateralis

• CA3 cell —> recieves input from dentate gyrus

• dentate gyrus —> receives input from entorhinal cortex, projects to C3

ability of synapses (connections btw neurons) to strenghthen / weaken over time in response to increase / decrease in their activity

—> fundamental for learning and memory

simultaneous activation of neurons —> increase in strength of synaptic connection

‘Neurons that fire together get wired together’

• PTP (post-tetanic potentiation)

• STP (short-term potentiation)

• LTP (long-term potentiation)

• LTD (long-term depression)

• depotentiation

persistent increase in synaptic strength that can rapidly induced by brief neural activity

found in mammalian…

• neocortical regions

• subcortical nuclei

• peripheral nervous system

• AMPA

  —> homotetramers / heterotetramers

  subunits: GluA 1-4

• NMDA

  —> heterotetramers

  subunits: GluN1 + one of GluN2

• GABA

  —> heteropentamers

  subunits: a, b, g, d type

  
  

• Agonists —> Glutamate + NMDA

• Coagonists —> Glycine + D-serine

• Antagonists —> AP5

• Channel Blockers —> Mg²⁺

Na⁺ and Ca²⁺ can pass into the cell

K⁺ can pass out of the cell

• Agonists —> Glutamate + AMPA

• Antagonists —> NBQX

Na⁺ (and small amounts of Ca²⁺) can pass into the cell

K⁺ can pass out of the cell

interact with GRIP, SAP-97 and others

Synaptic strength and Ca++ permeability of glutamate postsynaptic complexes

on anaesthesized rabbits’ hippocampus

• Brief high-frequency stimulation of the perforant pathway

• Produced long-lasting enhancement of the extracellular recorded field potential

• stimulating electrode in Schaffer Collateralis

• recording pipette in CA1

1. single puls to Schaffer in CA1 recorded —> baseline

2. 100Pulses/100Hz delivered to Schaffer

3. increased EPSP in CA1 after single pulse

record from a single cell

—> clamp cell at different potentials

clamp (Klemme)

1. Glutamate released from postsynaptic neuron

2. Glutamate binds to specific receptors (AMPA, NMDA)

   —> ion channels open

   —> Na⁺ and Ca²⁺ in neuon

   —> depolarization and generation of EPSP

3. Ca²⁺ influx through NMDA receptors activates pathways

   —> long-term changes in synaptic strength (LTP)

4. terminated by removal of glutamate

1. Glutamate release

2. Glutamate activates NMDA, AMPA receptors

3. AMPA receptors depolarize membrane

   —> removing Mg²⁺ block from NMDA receptors

4. Ca²⁺ enters through NMDA receptors

5. Ca²⁺ activates kinases

6. AMPA receptors are inserted

7. Dendritic spines grow and stabilize

8. Long-term changes in gene expression and protein synthesis stabilize LTP

only during depolarization.

• active synapse

• depolarization of postsynaptic neuron

• removal of Mg2+-block

when NT binds to depolarized post synaptic membrane

• dendritic spines are split after LTP —> new growth

• split snapses —> production of new synapses

• LTP1 ( < 3-6 hours)

  • blocked by protein kinease inhibitors

  • not blocked by protein synthesis inhibitors

• LTP2 (hours)

  • blocked by translational inhibitors

• LTP3 (days)

  • animal unanaesthesized at time of induction

  • may require gene expression

• LTP results in insertion of new AMPA receptors into dendrite

• more glutamate receptors —> stronger potentials in active synapse

• AMPA receptors located inside dendrite —> move to tips of spines after LTP induction

by adrenergic receptor activation

better memories when paying attention bc of higher emotional stimulation

—> small amount of stress helps to learn better

• Place cells —> always fire at specific location

• Head Direction cells —> always fire when in certain orientation to landmark (internal compass)

• Grid cells —> cells fire in grids of hexagons (create cognitive maps of space)

• Border cells —> mostly active when approaching border

• Speed cells —> firing rate follows animals speed

• learning and memory

• explciit memory, long-term memory

• spatial processing and navigating

main player: AMPA and NMDA receptor

removal of Mg2+ block and Ca2+ influx through NMDA receptors

Ca2+ activates Kineases

neuronal response of postsynaptic site is potentiated

update the estimate of location using two types of inputs:

• path integration (grid cell)

• sightings

place, grid, border and head direction cells form complex network insde hippocampus —> comprehensive positioning system (inner GPS)

place and grid cells provide system for anchoring our memories

grid cell system as primary concept —> Non-spatial things