PSYC1017 Lecture 8 Notes

Behavioural Neuroscience

Outline

  • The case of HM
  • What HM could learn
  • The Declarative and Non-Declarative distinction
  • Spatial Learning and the Hippocampus
  • What is happening at the neuronal level? Long Term Potentiation
  • Three store model of memory

Reading

  • Carlson and Birkett, Foundations of Behavioural Neuroscience, Chapter 13, pages 306-313, 320-326, 328-332.

Aim

  • Introduce different types of memory.
  • Explain the role of the hippocampus in memory consolidation.
  • Explain LTP and how it strengthens synapses, underlying learning-related brain changes.

Objective

  • Describe different types of memory.
  • Explain why hippocampus destruction caused anterograde amnesia in HM.
  • Describe neuronal changes explaining how associations are stored.

HM: Henry Molaison (1926-2008)

  • Underwent brain operation in 1953 to correct a seizure disorder.
  • Developed profound amnesia, losing the ability to form new memories (anterograde amnesia).
  • Participated in hundreds of studies, contributing to the understanding of learning, memory, and physical dexterity.

Bi-lateral Medial Temporal Lobectomy

  • Patient HM reported by Scoville and Milner (1957).
  • HM suffered from epilepsy and had medial temporal lobe removed to control the seizures.
  • Part of the brain removed was HM's hippocampus.
  • Treatment produced memory impairments (Antergrade amnesia).
  • Amongst HM's difficulties was finding his way around his new neighbourhood

Anterograde and Retrograde Amnesia

  • Retrograde Amnesia: Cannot remember events prior to brain damage.
  • Anterograde Amnesia: Cannot later remember events that occur after brain damage.

HM's Memory Abilities

  • Could remember things that happened before his operation.
  • Could repeat 7 numbers back to the experimenters as long as he kept repeating the numbers.
  • If he was distracted, he would forget the numbers.
  • The next day he would not remember the task or the experimenters.

Types of Memory

  • Sensory Memory
    • Briefly remembers initial sensations of environmental stimuli.
    • Length ranges from fractions of a second to a few seconds.
    • Occurs in each of the senses.
  • Short-Term Memory
    • Contains information from sensory memory if meaningful or salient enough.
    • Length ranges from seconds to minutes.
    • Involves rehearsal.
    • Capacity is limited to a few items.
    • Chunking.
  • Long-Term Memory
    • Contains information from short-term memory that is consolidated.
    • Relatively permanent.
    • Lasts for minutes, hours, days, or decades.
    • Strengthened with increased retrieval.
    • Two major categories: Nondeclarative memory and Declarative memory.

Three-Store Model of Memory

  • Sensory Input → Sensory Memory (Unattended information is lost)
  • Sensory Memory + Attention → Short-Term Memory (Unrehearsed information is lost)
  • Short-Term Memory + Maintenance Rehearsal/Encoding → Long-Term Memory (Some information may be lost over time)
  • Long-Term Memory can send information back to Short-Term memory via retrieval.

Things that HM could learn

  • Motor Learning: Mirror drawing
  • Perceptual Learning: Examples of Broken Drawings (Source: Gollin, E. S. (1960). Developmental studies of visual recognition of incomplete objects. Perceptual and Motor Skills, 11(3), 289–298.)
  • Classical Conditioning: we define two stimuli – the conditioning (ed) stimulus (CS) and the unconditioned stimulus (US) And two responses – the conditioned response (CR) and the unconditioned response (UR)

Human eyelid conditioning

  • The human eyelid can be classically conditioned.
  • Unconditioned stimulus: airpuff
  • Conditioned stimulus: tone
  • Conditioned response: eyeblink

Classical conditioning in the real world

  • Chronic use of Drugs
  • Conditioned Tolerance
  • Crowell, Hinson & Seigel, 1981
    • Saline: No reaction
    • Alcohol Test: Hypothermia
    • Alcohol: Hypothermia reduced due to tolerance to alcohol

Changes at the Neuronal level

Hebb's Law
  • Neuron in somatosensory system
    • Puff of air to the eye
  • Neuron in auditory
    • 1000-Hz tone
    • Synapse P (strong)
    • Synapse T (weak)
  • Blink

Woodruf-pak delay conditioning

  • CS-US trials
  • Delay conditioning procedure used by Woodruf-Pak (1993, Behavioral Neuroscience, 107, 911-925) for conditioning HM.
  • CS alone trials
  • time = 400ms; CS → time = 100ms; US

Woodruf-pak results

  • EYEBLINK CLASSICAL CONDITIONING IN H.M.
  • DELAY CLASSICAL CONDITIONING PARADIGM
  • CRs in Paired CS-US Trials
  • CRs in CS-Alone Trials

Long-Term Memory

  • Declarative Memory
    • Also called explicit memory
    • Memory of events and facts we can think and talk about
    • Not simply verbal, but like a video
    • Includes episodic memories (context) and semantic memories (facts) spatial memories (in relation to other things in the environment)
  • Nondeclarative Memory
    • Also called implicit memory
    • Includes memories that we are not necessarily conscious of
    • Operates automatically and controls motor behaviors
    • Such as riding a bike, throwing a ball, dancing

Human Anterograde Amnesia

  • Although people with amnesia can learn to perform tasks, they do not remember learning them
  • People with anterograde amnesia are unable to form declarative memories, but can form nondeclarative memories

Examples of Declarative and Nondeclarative Memory Tasks

  • Declarative Memory Tasks
    • Remembering past experiences
    • Learning to recognize broken drawings
    • Remembering facts
    • Remembering where things are in relation to other places in an environment
  • Nondeclarative Memory Tasks
    • Classical conditioning
    • Motor Learning (blank)
    • Operant conditioning

Types of Memory (Figure 13.7)

  • Human memory
    • Sensory memory (< 1 sec)
    • Short-term memory (< 1 min)
    • Long-term memory (lifetime)
      • Declarative memory (facts, events)
        • Episodic memory (events, experiences)
        • Semantic memory (facts, concepts)
      • Nondeclarative memory (skills, tasks)

HM’s Antegrade Amnesia

  • What he couldn’t do
    • Store new Declarative memories
  • What he could do
    • Store new Non-declarative ones

Bilateral Amygdala Damage in Patient H. M.

  • Note the lesions in H. M.’s temporal lobe and hippocampus that differ from a typical brain.

Hippocampus (little seahorse Lewis, 1923)

  • Major Components of the Limbic System
    • Fornix
    • Corpus callosum
    • Mammillary body
    • Amygdala
    • Hippocampus
    • Limbic cortex
    • Cerebellum

Evidence from Human Experiments

  • Maguire et al (1998) Journal of Cognitive Neuroscience, 19, 61-76. showed activity in the right hippocampus in participants navigating around a virtual town
  • Maguire, Frackowiak and Frith (1997) Journal of Neuroscience, 17, 1703-1710
  • Had taxi drivers talk about their routes and monitored hippocampal activity

Damage limited to the Right hippocampus causes spatial impairment

  • Feigenbaum and Morris (2004) Neuropsychology, 18, 462-472
  • Luzzi et al. (2000) Cortex, 36, 427-434. reported patient with damage to the right parahippocampal gyrus could only find his room by counting the doors from the end of the hall
  • Barkas, L. J., Redhead, E. S., Taylor, M., Shtaya, A., Hamilton, D. A., & Gray, W. P. (2012). Brain, 135, 2358–2374. doi:10.1093/brain/aws176. reported both rats and epilepsy patients with scarring caused by seizures in the right hippocampus could not use spatial cues to locate object.

Morris Water Maze (Morris et al, 1982, Nature, 297, 681-683 )

  • Experimentals vs Controls.

Not all spatial ability is controlled by the hippocampus

  • Egocentric v Allocentric
  • Entorhinal cortex controls egocentric guidance (McDonald & White, 1995) Behavioral Neuroscience, 109, 579-593
  • Barkas et al (2010) Behavioural Brain Research, 280, 535-544. Epilepsy patients with lesions to right hippocampus impaired in allocentric but not egocentric navigational task

Egocentric v Allocentric memory

  • Morris et al. (1982) Nature, 297, 681-683.
  • The Morris water maze.
    • Variable start positions (relational task)
    • Constant start position (stimulus-response task)
  • Variable start positions = Allocentric
  • Constant start position = Egocentric
  • Lesion vs Control

Role of the Hippocampal Formation in Consolidation of Declarative Memories

  • Hippocampus receives information about what is going on from the sensory and motor association cortex and processes this information
  • Through its efferent connections with these regions, it modifies the memories that are being consolidated, linking them together so we can remember the relationships among the elements of the memories
  • The Hippocampus places episodic memories in the right order so they make sense
  • In terms of spatial information the entorhinal cortex tells you which direction to go but your hippocampus tells you where you are in relation to the things around you

Summary

  • Damage to right Hippocampus means we can’t learn where things are in the world
  • Entorhinal Cortex can tell us which direction to go but we need Hippocampus to work out where we are in the first place
  • The Hippocampus co-ordinates and orders our memories so they can be consolidated in long term memory

Changes at the Neuronal level

  • Evidence of Long term potentiation
  • Hebb's Law

How do messages travel along the neuron

  • Membrane potential (mV) with Depolarization and Hyperpolarization.

Long term potentiation - procedure

  • Record from dentate gyrus
  • Stimulate axons in perforant path
  • Field CA3 → Field CA1 → Dentate gyrus → Entorhinal cortex

Key Concepts: Long-Term Potentiation

  • SC → MF
  • Before long term potentiation the population EPSP.
    record then stimulate.

Long term potentiation - result

  • Before long-term potentiation vs After long-term potentiation.
  • 1 hour, 24 hours, 48 hours, 72 hours, 96 hours
  • Population EPSP

The role of Summation in Long-Term Potentiation

  • Membrane potential
  • High vs Low
  • Threshold for establishment of long-term potentiation
  • Low rate of stimulation does not depolarize membrane sufficiently

What is actually happening at the neuron? Role of Glutamate

  • Long-term potentiation (LTP) is a series of synaptic changes
  • LTP among glutamate synapses in the hippocampus help establish conditioned responses
  • Synaptic changes in the glutamate system increase the excitatory post synaptic potential (EPSP) to the postsynaptic cell
  • Glutamate bonds with two types of Receptors NDMA and AMPA receptors in the Post synaptic membrane
  • When Post synaptic membrane is at resting potential (-70mv) the NMDA receptors are blocked by Magnesium
  • Glutamate will only open AMPA receptors which let in Sodium (NA+) molecules
  • The +ve NA molecules will depolarize the neuron which unblocks the NDMA receptors allowing Calcium ions into the neuron as well.

Synaptic Changes in NMDA and AMPA Receptors in LTP

  • NMDA Receptor
  • AMPA Receptor
  • Dendrite
  • Mg++Mg^{++}
  • Glutamate
  • Na+Na^{+}

The NMDA Receptor

  • The NMDA receptor is a neurotransmitter- and voltage-dependent ion channel.
    • When the postsynaptic membrane is at the resting potential, Mg2+Mg^{2+} blocks the ion channel, preventing Ca2+Ca^{2+} from entering.
    • When the membrane is depolarized, the magnesium ion is evicted. Thus, the attachment of glutamate to the binding site causes the ion channel to open, allowing calcium ions to enter the dendritic spine.

Synaptic Strengthening

  • When the conditions for long-term potentiation are met, Ca2+Ca^{2+} ions enter the dendritic spine through NMDA receptors. The calcium ions activate enzymes in the spine.
  • The activated enzymes cause AMPA receptors to move into the spine.
  • An increased number of AMPA receptors in the postsynaptic membrane strengthens the synapse.

Section Summary

  • Hebbs Law – Paired stimuli strengthen shared synapse
  • Evidenced by Long Term Potentiation
  • Glutamate unblocks NDMA receptors and creates more AMPA receptors creating LTP

Next week’s lecture

  • Communication part 1
  • Non-Human animal communication – Do animals Lie?
  • Reading Mitchell, R. W., & Anderson, J. R. (1997). Pointing, withholding information, and deception in capuchin monkeys (Cebus apella). Journal of comparative psychology (Washington, DC: 1983), 111(4), 351. doi: 10.1037/0735-7036.111.4.351