Emotions: Learning, Memory + Cognition

Synaptic Plasticity Summary

• Long-Term Potentiation (LTP)

  • Strengthens synapses.

  • Makes it more likely that adjacent neurons will fire together.

• Long-Term Depression (LTD)

  • Weakens synapses.

  • Makes it less likely that adjacent neurons will fire together.

• Very well studied in vitro, especially in the Hippocampus.

• Best established model of learning at the cellular level.

  • Been difficult to demonstrate direct link in vivo.

Role of the Hippocampus: Health and Disease

• Normal, age-related cognitive decline:

  • Many, but not all, cognitive functions decline with age.

  • Spatial memory is one of these.

    • Spatial navigation task: finding objects in a maze (museum).

• How does the Hippocampus age?

  • Does not seem to get smaller (although evidence is mixed).

  • Retains the same number of neurons (although evidence is mixed).

  • Functional connectivity is impaired.

    • Retrieval is not as strong (generally).

  • LTP does not last as long, and is not as strong (rat studies).

  • Impaired retrieval of spatial maps (rat studies).

Ventricular System

• Ventricles filled with Cerebrospinal fluid (CSF).

  • Produced by ependymal cells which line ventricles.

  • Functions:

    • Shock absorber.

    • Nutrient supply.

    • Waste flush.

  • Volume: ~125ml at any one time, ~500 ml produced per day.

  • Anatomical Landmark.

Alzheimer’s Disease

• Common signs:

  • Memory loss (related to the hippocampus).

  • Poor judgment leading to bad decisions.

  • Loss of spontaneity and sense of initiative.

  • Taking longer to complete normal daily tasks.

  • Repeating questions.

  • Trouble handling money and paying bills.

  • Wandering and getting lost (related to the hippocampus).

  • Losing things or misplacing them in odd places (related to the hippocampus).

• Loss of neurons in various brain regions:

  • Particularly the hippocampus and cerebral cortex.

• Cause and Treatment

  • Accumulation of misfolded proteins in certain brain regions:

    • Cholinergic nuclei, hippocampus, and frontal cortex.

    • Beta-amyloid (amyloid plaques).

    • Tau (neurofibrillary tangles).

    • Accumulation is toxic – mechanisms unclear.

    • Some genetic risk.

  • Memantine – slows excitotoxicity.

  • Acetylcholinesterase inhibitors – mitigate loss of ACh.

Brain Cholinergic System

• Key nuclei:

  • Basal forebrain.

  • Brainstem tegmentum.

• Project across the brain:

  • Cortex.

  • Hippocampus.

  • Thalamus.

  • Etc.

• Neuromodulatory functions:

  • Memory.

  • Cognition.

  • Arousal.

Limbic System

• Does not exist as a discrete entity?

• Described in textbooks as an ‘emotion system’.

  • Concept comes from the outdated ‘Triune Brain’ theory.

    • Lizard Brain, Limbic System, Neocortex.

    • (Concept is overly simplistic, but some concepts are useful).

  • Textbook descriptions include some important brain regions that are involved in Learning and Memory.

    • Learning about emotions.

  • Limbus means border, forms a ‘ring’ around the brain stem and corpus callosum on the medial walls of the brain.

• Components:

  • Hippocampus.

  • Amygdala.

  • Hypothalamus.

  • Fornix.

  • Thalamus.

  • Mamillary Bodies.

  • (Cingulate Gyrus).

  • (Orbitofrontal Cortex).

Amygdala

• Functions:

  • Salience, ‘Vigilance’.

    • Amygdalofugal pathway to/from the thalamus.

  • Stimulation results in fear + aggression.

  • Recognizing fear in other people.

  • Learning about cues.

    • Best understood is fear/danger.

    • (More than just fear).

• Clinical relevance:

  • Anxiety disorders.

    • Hyperactive.

    • Hypervigilance (PTSD).

  • Bilateral lesions - Kluver-Bucy Syndrome (very rare).

    • Reduced fear/docility.

    • Visual agnosia.

    • Pica.

    • Hyperorality and Hypersexuality.

    • Normally caused by surgical complications or HSV.

Fornix

• Hippocampal output.

• Connects left and right hippocampus.

• Helps hippocampus function.

• Damage is rare.

  • Looks like hippocampal damage.

  • Anterograde Amnesia.

Mammillary Bodies

• Korsakoff’s syndrome

  • Irreversible damage to Medial thalamus + Mamillary bodies.

  • Most common cause is vitamin B1 deficiency.

    • Chronic alcoholism.

      • Unable to absorb vitamin B1 (thiamine).

      • Direct toxicity of alcohol.

  • Anterograde AND retrograde amnesia.

  • Confabulation (Confusion between memory and imagination).

  • Little or no recovery.

  • Precise role for mammillary bodies in learning and memory?

Hypothalamus

• Start of a physiological output from the brain.

  • Hypothalamus-Pituitary-Adrenal (HPA) axis.

  • Hormonal outputs – especially stress hormones.

  • Also wired into the brainstem, autonomic system.

• Functions:

  • Thermoregulation.

  • Hunger, thirst, etc.

• The rest of the limbic system is trying to persuade the hypothalamus to do what the limbic system wants.

Olfactory Pathways

• Don’t (really) go through the Thalamus.

  • Thalamus has limited involvement.

• Connect to limbic/memory systems.

  • Is a very powerful memory cue.

Pavlovian (Classical) Conditioning

• Amygdala important for learning conditioned cues.

  • Best understood role is learning about danger and fear.

  • Probably important for all cues, not just fear-inducing.

  • Learning about danger is really important.

• Extinction of Classical Conditioning

  • Learning about cues in our environment that predict serious danger is very important and normal.

  • This learning is very strong.

  • Learning when those cues are not associated with danger takes time.

  • This ‘forgetting’ is new learning.

    • The old memory is not ‘lost’.

    • New memory is ‘stronger’, more salient.

Post-Traumatic Stress Disorder (PTSD)

• Definition: PTSD is associated with significant trauma involving the risk of death or serious harm.

• Re-experiencing Trauma:

  • Sufferers re-experience the trauma through triggers or reminders (conditioned stimuli).

  • This is normal for a few weeks post-trauma, but if it persists, it becomes PTSD.

• Symptoms:

  • Hyperarousal and hypervigilance ('on edge').

  • Avoidance behaviors.

  • Emotional numbing.

• Neurological Differences in PTSD:

  • Amygdala: Hyperactive (related to fear and cues).

  • Prefrontal Cortex: Hypoactive and potentially smaller (related to 'forgetting').

  • Hippocampus: Potentially smaller with reduced functionality, contributing to difficulties in forming new memories and processing contextual information.

Summary Part 1

• 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.

    • Code can be modified to allow finer distinctions.

      • Pattern separation.

• Hippocampus also very important for spatial memory.

• Function declines with age.

• Decline is accelerated in Alzheimer’s Disease.

Summary Part 2

• Limbic System is defined in the literature as an ‘emotion system’.

  • Many subcortical structures.

  • Learning about emotions, vigilance, and salience.

  • Implicated in memory and anxiety conditions.

• PTSD is associated with re-experiencing traumatic events.

  • Complex interplay between the amygdala, hippocampus, and PFC.

  • Can be treated by Behavioral therapies.

  • Sufferer knows something is wrong.