Lecture 13: The Hippocampus

Hippocampus

- Is essential for memory formation

- Simple and layered, makes it ideal for studying long term potentiation (LTP) and long term depression (LTD) --> key for learning/memory

Famous Case -- Patient H.M.

Lost ability to form new memories after both hippocampi are removed

Where is the Hippocampus?

- Lies in medial temporal lobe, under parahippocampal gyrus

- Fornix = major fiber tract carries output from hippocampus, connected by anterior commissure

Names and Appearance

- Hippocampus

- Cornu ammonis (ammons horn)

- Fields CA1-CA3

Cornu ammonis (ammons horn) -- Nomenclature

ram horn shape

Hippocampus -- Nomencalture

- Seahorse (seen in coronal slices)

- Most heavily studied structure

Fields CA1-CA3 -- Nomenclature

subdivisions of pyramidal cell zones in Cornu ammonis

Principal Hippocampal Cells

- Dentate Gyrus: granule cells (excitatory)

- Cornu Ammonis (CA1-CA3): pyramidal cells (excitatory)

Three Layers of CA Fields

- Stratum pyramidale

- Stratum Radiatum and Stratum Lacunosum Moleculare

- Stratum Oriens

Stratum pyramidale (Pyramidal cell Layer)

Cell bodies of pyramidal cells

Stratum Radiatum and Stratum Lacunosum Moleculare (Molecular Layer)

apical dendrites (input zones)

Stratum Oriens (polymorphic layer)

basal dendrites + axons of pyramidal cells

5 Synapse Circuit

Important synaptic loop in consolidation of memories

5 Synapse Circuit (Entorhinal Cortex --> Hippocampus and Back)

- Preforant Path: Entorhinal cortex --> dentate gyrus granule cells

- Mossy fibers: Dentate gyrus --> CA3 pyramidal neurons

- Schaffer Collaterals: CA3 --> CA1 pyramidal neurons

- CA1 --> subiculum

- Subiculum --> Entorhinal cortex (loop complete)

- Glutmate is main neurotransmitter throughout this loop

Other Outputs via Fornix

- To mammillary bodies --> thalamus (via mammillothalamic tract) --> cingulate gyrus --> back to entorhinal cortex = Papez circuit (emotionally linked memories)

- To contralateral hippocampus via commissural fibers

- To cholinergic cells in basal forebrain (send ACh back to hippocampus to enhance LTP)

Acute Slice Model

- Animal hippocampus cells studied in vitro

- Slices are placed in artificial cerebrospinal fluid and visualized with microscope

- Two methods record activity

Methods to Record Activity

- Patch Clamp: records from single cells

- Field Electrode: records from a group of neurons --> fEPSPs

Excitatory Synaptic Transmission -- Receptors

- AMPA

- Kainate

- NMDA

AMPA

Main excitatory response (Na+ in, K+ out)

Kainate

Similar to AMPA, but more specialized

NMDA

- Needs depolarization + glutamate to activate

- Blocked by Mg2+ at rest

- When unblocked, allows Ca2+ to enter --> triggers LTP or LTD

fEPSP Components

- Stimulus artifact: from electrical pulse

- Fiber volley: firing of axons (Schaffer collaterals)

- fEPSP: synaptic potential (inverted relative to intracellular EPSP)

LTP Protocol

- Record baseline fEPSPs

- Apply tetanic stimulation (100Hz, 1 sec)

- Continue recording: fEPSPs should be larger and faster, lasting hours --> LTP

Mechanism of LTP

- Ca2+ enters via NMDA receptors - Triggers insertion of AMPA receptors into the postsynaptic membrane

- More AMPARs = Stronger EPSPs = potentiated synapse

LTD

- Weak stimulation (1-5Hz) = smaller Ca2+ influx

- Leads to the removal of AMPARs --> weaker synapse (depression)