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.