SA

Encoding Part 2 - Lecture 4

Introduction

  • This lecture focuses on the hippocampus and its role in storage, modification, and indexing of memories.

Information Flow in Learning and Memory

  • Sensory information flows from the thalamus to cortical association areas.
  • From cortical association areas, information goes to parahippocampal and rhinal cortices.
  • These cortices then project to the hippocampus.
  • The hippocampus is involved in encoding. It connects to the fornix, which leads to the mamillary bodies (hypothalamus).
  • Retrieval of information also involves the hippocampus.

Medial Temporal Lobe Anatomy

  • The medial temporal lobe includes:
    • Hippocampus
    • Entorhinal cortex
    • Perirhinal cortex
    • Parahippocampal cortex
  • Parahippocampal and perirhinal cortices serve as connections between association cortices and the hippocampus.

Removal of the Medial Temporal Lobe

  • Removal results in severe anterograde amnesia.
  • H.M. (Henry Molaison) had his medial temporal lobe removed to alleviate epileptic seizures, resulting in anterograde amnesia.

Functions of the Hippocampus

  • Formation of declarative/explicit memories, which are ultimately stored in the cortex.
  • Spatial memory/learning, helping in knowing one's location in space.
  • The hippocampus is often affected early in Alzheimer's disease.
  • It is an active site of neurogenesis.
  • It comprises multiple sub-regions.

Encoding Patterns

  • Pattern Completion: Recognizing something from a partial representation.
  • Pattern Separation: Learning to distinguish between similar patterns.
  • The hippocampus is crucial for both pattern completion and separation.
  • These processes are not limited to visual memories.

Neuronal Physiology: Core Principles

  • The nervous system uses electrical and chemical signals for information transfer.
  • Neurons are the primary electrical cell type.
  • The electric signal travels along neurons as an action potential.
  • The chemical signal travels between neurons as neurotransmitters.
  • Excitatory neurotransmitters increase the probability of the target neuron firing an action potential.
  • Inhibitory neurotransmitters reduce the probability of the target neuron firing an action potential.
  • The human brain contains approximately 86 billion neurons and 86 billion non-neuronal cells.

Neuronal Code

  • The 'code' may involve:
    • Which neurons fire.
    • What causes them to fire.
    • How often they fire.
    • How long they fire for.
    • Where they project to.
    • How many other neurons they are connected to.
    • Numbers/types of neurotransmitter receptors.

Hippocampal Indexing

  • Forms the basis for retrieval using pattern completion and pattern separation.
  • Pattern of neuronal activity from the cortex activates a specific subpopulation of neurons in CA3.
  • CA3 neurons are densely and reciprocally connected.
  • Partial input can activate the entire group of CA3 neurons.
  • Connections between neurons in this group can be modified during learning.

Synaptic Plasticity

  • Synaptic plasticity is the cellular basis for learning and memory.
  • Neurons that fire together wire together.

How Neurons Fire Action Potentials: A Brief Revision

  • Resting Membrane Potential:
    • The neuronal cell membrane at 'rest' has an electrical potential.
    • Ion concentrations inside and outside the cell:
      • Na^+: Intracellular - 15 mM, Extracellular - 150 mM
      • K^+: Intracellular - 100 mM, Extracellular - 5 mM
      • Ca^{2+}: Intracellular - 0.0002 mM, Extracellular - 2 mM
      • Cl^-: Intracellular - 13 mM, Extracellular - 150 mM
      • A^-: Intracellular - 385 mM, Extracellular - 0 mM
    • Two forces at work:
      • Electrical force (opposites attract)
      • Chemical force (concentration gradient)
  • Action of Excitatory Neurotransmitters:
    • Neurotransmitters from the presynaptic neuron bind to ligand-gated channels, allowing ions (e.g., Na^+) to flow into the postsynaptic neuron.
  • Action Potentials as Electrical Signals:
    1. Presynaptic neuron releases neurotransmitter.
    2. Enough ligand-gated channels open.
    3. Membrane reaches threshold.
    4. Action potential fires.

Long-Term Potentiation (LTP)

  • Frequent firing strengthens synapses.
  • Brief, intense firing by presynaptic neuron:
    • Abundant glutamate release.
    • Causes changes in the postsynaptic neuron.
    • Opens NMDA-type glutamate receptors.
    • Increases expression and insertion of AMPA-type glutamate receptors.
    • Strengthens the synapse and increases the likelihood that neurons fire together.
    • Changes are long-lasting due to calcium influx prompting gene expression.
    • Best understood in the hippocampus (CA3 to CA1 synapse).

Long-Term Depression (LTD)

  • Connections between neurons become weaker.
  • Prolonged, low-intensity firing of presynaptic neuron:
    • Pre- and postsynaptic neurons do not fire together.
    • Decreased expression/insertion of postsynaptic AMPA receptors.
    • Decreased presynaptic glutamate release.
    • Also occurs across the brain but is not as well understood as LTP.

From Synapse to Code to Memory

  • One theory: the 'code' is a firing pattern of a specific group of neurons in a hippocampal region (CA3).
  • Firing pattern in association cortices activates that specific group.
  • Partial firing still activates the full group.
  • The firing of the code group then recreates the representation in the association cortices.
  • The members of the group and their firing pattern can be modified by LTP and LTD, allowing for the formation of distinct groups as part of pattern separation.

Boosting Memory

  • Eating glutamate or stimulating NMDA and AMPA glutamate receptors is generally not advised.
  • Systemic stimulation can cause seizures.
  • Too much glutamate is excitotoxic and can cause cell death (e.g., in stroke, Alzheimer's).
  • Blocking NMDA-R with Memantine (Ebixa) can be moderately effective.

Spatial Memory

  • Types of Spatial Representation:
    • Allocentric (non-egocentric): A map of the environment (object-to-object) in the hippocampus.
    • Egocentric: Where am I in the environment (me-to-object) using left/right, up/down, etc., in the posterior parietal cortex + prefrontal cortex.

Place Cells

  • Pyramidal neurons in the hippocampus (CA1 + CA3).
  • Activated by allocentric environmental cues (visual, olfactory, other senses).
  • Also activated by 'replay' of cues (thinking about the map).
  • Encode a 'place field' that can change (plastic).
  • Some are spatially oriented (front, back, etc.).

Other Navigational Neurons

  • Head Position Cells: Subiculum; fire when oriented toward a specific direction.
  • Border Cells: Place cells activated by barriers.
  • Reward-Place Neurons: Learn about a reward in a particular place, bringing together 'where is it' and 'what is it'.

Grid Cells

  • Located in the entorhinal cortex.
  • Hexagonal map allows efficient coding of space.
  • Adjacent grid cells map adjacent grids.
  • May measure distance.
  • Involved in 'Dead Reckoning' or 'Path Integration': calculating current position relative to a previous position.
  • These spatial representations also apply in 3D, such as in bats.

Summary

  • The hippocampus stores memory as a neuronal 'code' (specific group of neurons firing in a specific way).
  • Activated by projections from the association cortices (pattern completion).
  • The code can be modified to allow finer distinctions (pattern separation).
  • The hippocampus is also vital for spatial memory.