16/24: Cellular Cognition

learning

→ refers to the process by which experiences change our nervous system and by extension, our behaviour

• Memory (memories, memory traces, memory engrams) → the changes resulting from learning — stored knowledge

  • Transient (short-term) or durable (long-term)

  • Explicit (conscious) or implicit (unconscious)

  • Personal (episodic) or impersonal (semantic)

  • Retrieval → process of accessing memories, whose application = intelligence

  • Feedback → input-output information that makes learning more effective and efficient; improvement leads to optimization

neuronal plasticity

→ refers to the ability of the nervous system to change and adapt — cellular basis of long-term memory

Measurements (via brain slice recordings):

• Intrinsic excitability → the # of APs a neuron exhibits in response to depolarizing electrical current injections

  • Reflects precise composition of ion channels on a membrane (strongly affected by ↑ # of K+ leak channels)

  +

• Synaptic strength → size of the response in a post-synaptic neuron when a pre-synaptic neuron has an AP

synaptic plasticity

→ refers to the changes in strength of the synaptic connection between adjacent neurons (i.e., delta synaptic strength)

• Enduring, long-term changes often involve physical changes in the size of pre- and post-synaptic membranes

  • Pre-synaptic changes: # of vesicles, used vesicles, release of vesicles

  • Post-synaptic changes: # of receptors, ligand sensitivity, binding effects

• Excitatory post-synaptic potential (EPSP) → depolarization as a post-synaptic response

  • Often involved with improving synaptic strength

habituation

→ type of non-associative learning; reduced physiological or behavioural responding to a repeated stimulus

• ex. Aplysia sea slugs reflexively withdraw their gill whenever their siphon is touched. After repeated siphon touches, the magnitude of the gill withdrawal reflex will reduce to a point of indifference.

Significant effects:

• ↓ Motor neuron response (due to ↑ sensory neuron)

• ↓ Pre-synaptic vesicles (available and/or being released)

sensitization

→ type of non-associative learning; when exposure to a strong (and often painful) stimulus results in heightened responses to other stimuli

long-term potentiation

LTP → in regards to synaptic plasticity; an enduring ↑ in synaptic strength — improving

• Elicited by repeatedly stimulating a neuron’s inputs with high-frequencies

  • Tetanic ex. 100 Hz, for 1 second, repeated 4 times

  • Passing threshold stimulation (summation of EPSPs/depolarizations) enables post-synaptic neurons to spike

• Initiated on post-synaptic side (w/ ↑ receptors)

  • Nitric oxide → retrograde signaling molecule that triggers complimentary changes on pre-synaptic side (↑ neurotransmitters released per spike)

long-term depression

LTD → in regards to synaptic plasticity; an enduring ↓ in synaptic strength — weakening

• Elicited by repeatedly stimulating a neuron’s inputs with low-frequencies

  • ex. 1 Hz, for 10 minutes

  • Insufficient threshold stimulation (summation of subthreshold responses/no depolarization) DOES NOT enable post-synaptic neurons to spike

• Initiated on post-synaptic side (w/ ↓ receptors)

  • Endocannabinoids → retrograde signaling molecule that triggers complimentary changes on pre-synaptic side (↓ neurotransmitters released per spike)

NMDA receptor

→ “coincidence” detector playing a large role in learning — ionotropic glutamate receptor located in almost every glutamatergic synapse in the brain

Rest-Hyperpolarized (< -40 mV):

• At rest, the ion channel pore is clogged by Mg2+ ions

Depolarization (> -40 mV):

1. Mg2+ ion blockade evicted

2. Binded glutamate can open ion channel

3. Ca2+ (and Na+) ions can enter neuron

AMPA receptor

→ ionotropic glutamate receptor that mediates most of the fast excitatory synaptic currents in the brain

• Often coincides with NMDA receptors (on most glutamate synapses)

Depolarization (> -40 mV): Na+ ions flow in when open, causing EPSPs

type II calcium-calmodulin kinase

CaMK-II → enzyme activated by Ca2+ ion influx through NMDA receptors

• Participates in intracellular signaling cascade establishing LTP by ↑ AMPA receptors in post-synaptic membrane

dendritic spine growth

→ for glutamatergic synapses, LTP correlates with the size of the dendritic spines + # of AMPA receptors

• Relatively easy to measure

associative long-term potentiation

→ describes the ↑ in synaptic strength that occurs in weak synapses that happen to be active when stronger inputs get the post-synaptic neuron to spike — Donald Hebb’s hypothesis applied;

• Hebb’s rule → the cellular basis of learning involves strengthening of synaptic connections that happen to be active when the post-synaptic neuron fires an AP

  • “Fire together, wire together”