Memory and Hippocampus

By:Mohammad Ali Ahmadi-PajouhAll Materials are from “Principals of

Neuroscience”Written by E. Kandel

In the Name of Allah

Amirkabir University of Technology

Animal Studies Help to Understand Memory

• Mortimer Mishkin and Squire produced lesions in monkeys.

• Damage to the hippocampus or the polymodal association areas in the temporal cortex caused damage to explicit memory for places and objects.

Neocortex

• Semantic (Factual) Knowledge Is Stored in a Distributed Fashion in the Neocortex

• That Includes objects, facts, and concepts as well as words and their meaning.

Hippocampus

• Damage Restricted to Specific Subregions of the Hippocampus Is Sufficient to Impair Explicit Memory Storage.

• Spatial Memory

• Verbal Memory

• The right hippocampus is activated during learning about the environment.

Taxi Derivers Test

• The right parahippocampal and hippocampal regions are significantly activated

• successful retrieval of words from long lists

A Brief View of Hippocampus Parts

NOTE!

• Thus, in processing information for explicit memory storage the entorhinal cortex has dual functions:– It is the main input to the hippocampus. – It is also the major output of the hippocampus

• Damage to this part affects not simply one but all sensory modalities.

• Alzheimer Disease (AD)

hippocampus’ three major pathways

• As first shown by Per Andersen, the hippocampus has three major pathways:

• (1) the perforant pathway,

• (2) the mossy fiber pathway

• (3) the Schaffer collateral pathway

Long-Term Potentiation

• In 1973 Timothy Bliss and Terje Lom

• each of these pathways is remarkably sensitive to the history of previous activity.

• This facilitation is called long-term potentiation (LTP).

The firing-rate patterns from four successive recording sessions

in a single cell

Place Cell

Associative Long-Term Potentiation Is Important for Spatial Memory

Radial Arm Maze

Cognitive Map

Thanks

Cellular Study of Memory Storage

• Elementary forms of learning: – Habituation– Sensitization– Classical conditioning

Habituation

• It Involves an Activity-Dependent Presynaptic Depression of Synaptic Transmission

• If the stimulus is neither beneficial nor harmful, the animal learns, after repeated exposure, to ignore it.

• It has both a short-term and a long-term form

Sensitization

• It Involves Presynaptic Facilitation of Synaptic Transmission

• Like habituation, sensitization has both a short-term and a long-term form.

• A synapse can participate in more than one type of learning and store more than one type of memory.

• Short-term habituation in Aplysia is a homosynaptic process; the decrease in synaptic strength is a direct result of activity in the sensory neurons and their central connections in the reflex pathway. In contrast, sensitization is a heterosynaptic process; the enhancement of synaptic strength is induced by modulatory interneurons activated by stimulation of the tail.

Classical Conditioning

• Involves Presynaptic Facilitation of Synaptic Transmission That Is Dependent on Activity in Both the Presynaptic and the Postsynaptic Cell.

• Rather than learning only about one stimulus, the organism learns to associate one type of stimulus with another.

Long-Term Potentiation in the Mossy Fiber Pathway Is Nonassociative

Rapid bidirectional switching of synaptic NMDA receptors.

• Neuron. 2007 Sep 6;55(5):779-85– Bellone C, Nicoll RA.– Departments of Cellular and Molecular Pharmacology and Physiology,

University of California, San Francisco, San Francisco, CA 94143, USA.

– Synaptic NMDA-type glutamate receptors (NMDARs) play important roles in synaptic plasticity, brain development, and pathology. In the last few years, the view of NMDARs as relatively fixed components of the postsynaptic density has changed. A number of studies have now shown that both the number of receptors and their subunit compositions can be altered. During development, the synaptic NMDARs subunit composition changes, switching from predominance of NR2B-containing to NR2A-containing receptors, but little is known about the mechanisms involved in this developmental process. Here, we report that, depending on the pattern of NMDAR activation, the subunit composition of synaptic NMDARs is under extremely rapid, bidirectional control at neonatal synapses. This switching, which is at least as rapid as that seen with AMPARs, will have immediate and dramatic consequences on the integrative capacity of the synapse.