B&B Mechanisms of memory Flashcards
HOW IS MEMORY ACQUIRED
AND STORED?
Change in the strength of neuronal connections
The neuron is the anatomical unit of the nervous system
Polarity of neurons
Neurons communicate at defined junctions - the synapse
What is Hebb’s postulate?
Correlated pre- and post -synaptic activities cause synapse strengthening & stabilization
• Uncorrelated activity between synaptic partners would weaken the connection
• “Cells that fire together, wire together.”
What is LTP?
long-term potentiation is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons
What occurs during the brief tetanus (1 s) that initiates LTP?
Induction
In what way are the synapses altered following LTP?
Expression
What are the 2 requirements for LTP?
(i) synaptic stimulation (neurotransmitter release) and
(ii) post-synaptic depolarisation
What is the role of NMDA receptors in induction of LTP?
Glutamate receptors mediate excitatory synaptic transmission
• NMDA receptors and AMPA receptors
• The NMDA receptor antagonist AVP blocked LTP (Collingridge et al. 1983)
• Multimeric complex of different subunits
• Ionotropic receptor binds glutamate
• Glycine is a co-agonist
• Ca2+/Na+ channel
• Magnesium blocks pore unless depolarized
• Ligand- and voltage-gated calcium permeable
receptors.
Describe the induction of LTP
Critically dependent on NMDA receptor activation - APV blocks LTP induction.
• Glutamate binding
• Sufficient depolarization of postsynaptic neuron
• Relief of Mg2+ block of ion channel
• Calcium influx
What are the phases of LTP?
• Early phase (LTP1, lasts 3 hours) Blocked by NMDA receptor antagonists Blocked by protein kinase inhibitors • Intermediate phase (LTP2) Blocked by gene transcription inhibitors Blocked by protein synthesis inhibitors • Late phase (LTP3, days) Requires protein translation and transcription Associated with extensive synaptic remodelling cAMP-dependent
What is the synaptic tag and capture hypothesis?
proposes that a strong stimulation of a synaptic pathway leads to two dissociable events: (a) local tag setting and (b) the synthesis of diffusible plasticity-related proteins (PRPs) plasticity related proteins
Frey & Morris (1997) Basis for input specificity & associativity Tag = local molecular changes at synapses that mark synaptic plasticity as having occurred. CaMKII-P Other candidates too
When the postsynaptic cell is
weakly depolarized by other
inputs: active synapses undergo
LTD instead of LTP. What is LTD?
long-term depression
an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus.
Describe the induction of LTD
Calcium influx via NMDARs activates
calcineurin (a phosphatase).
• Calcineurin (CaN) translocates to NMDA
receptor-associated proteins (AKAP79/150 &
PSD95) where it dephosphorylates protein
phosphatase one (PP1), which releases
Inhibitor-1 (I-1) from PP1-mediated tonic
suppression.
• Free I-1 dephosphorylates AMPARs at
Ser845, which decreases AMPAR stability at
the postsynaptic membrane
AMPA Receptors are tetamers (GluR1/2/3/4 subunits).
• Nearly all synaptic AMPA receptors contain WHAT?
• GluR1-only AMPA receptors are calcium permeable & drive
GluR1/2 receptors into the post synaptic membrane
GluR1 & GluR2.
What is metaplasticity?
Excitability can be globally up/down regulated without the loss of information stored at
specific synaptic sites
What role does the hypothalamus play in homeostasis?
- Drinking behaviour
- maintain blood volume and osmolality
- Feeding behaviour (energy metabolism)
- Short-term, meal size and timing
- Long-term, maintain body weight
- Body temperature
- Ovulation/sexual behaviours
- Circadian/circannual rhythms
- Control of the autonomic nervous system (ANS) – PVN/LH
- Stress response - PVN
Describe the sympathetic nervous system
“Week day” system
Fight, fright, flight & sexual behaviour
e.g. Increases heart rate Increases blood pressure Relaxes airways Increases glucose production Inhibits digestion Stimulates orgasm
Describe the parasympathetic nervous system
“Weekend” system
e.g. Decreases heart rate Decreases blood pressure Constricts airways Increases insulin production Stimulates digestion Stimulates sexual arousal
WHAT IS THE STRESS RESPONSE OF HYPOTHALAMICPITUITARY-ADRENAL (HPA) AXIS ?
CRH released from PVN (parvocellular neurons)
stimulates the anterior pituitary to secrete ACTH,
which enters the bloodstream and stimulates the
adrenal cortex to secrete glucocorticoids.
Glucocorticoids act to mobilize energy stores, increase
blood flow, etc.
Activated by both internal and external cues.
Negative feedback to PVN hypothalamus (short loop) &
hippocampus (long loop) – glucocorticoids only.
What are the 2 main theories of emotion?
James-Lange Theory (1884): Emotion is secondary to the physiological response to a stimulus
Why was this wrong?
Physiological changes were to slow to be the source of emotional feeling
• Similar physiological responses occur in different emotional states
• Emotions were experienced in the absence of physiological sensation
Cannon-Bard Theory (1927): Emotional responses can be independent of the physiological response
What is sham rage?
behavior such as biting, clawing, hissing, arching the back and “violent alternating limb movements” produced in animal experiments by removing the cerebral cortex, which are claimed to occur in the absence of any sort of inner experience of rage.
Removal of cerebral hemispheres but not hypothalamus -> sham rage. 1 or 1 & 2 • Behavior reversed with additional lesions in hypothalamus 3 • Hypothalamus may normally be inhibited by telencephalon.
Describe GLUCOCORTICOID RECEPTORS
the receptor to which cortisol and other glucocorticoids bind. The GR is expressed in almost every cell in the body and regulates genes controlling the development, metabolism, and immune response.
“Activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation, and this is both necessary and sufficient for the information storage underlying the type of memory mediated by the brain area in which plasticity is observed”
Describe necessity and sufficiency
Necessity Selective blocking/enhancing plasticity should block or enhance learning
Sufficiency Inducing plasticity at a discrete set of synapses should produce
a new memory
What 2 roles do NDMA receptors play?
- LTP
* Moment-to-moment synaptic transmission, independent of LTP
