Neural Plasticity
Nervous System is malleable learning occurs
Structural changes increased dendritic branching new synapses
Changes in synaptic efficiency Long-term potentiation Long-term depression ~
Neural Mechanism of Memory
Donald Hebb Short-term Memory
Change in neural activity not structural temporary
Reverberatory Circuits - cortical loops of activity ~
Hebb’s Postulate
Long-Term Memory required structural change in brain relatively permanent
Hebb Synapse use strengthens synaptic efficiency concurrent activity required
• pre- & postsynaptic neurons ~
Long-term Potentiation
According to Hebb rule use strengthens synaptic connection
Synaptic facilitation Structural changes Simultaneous activity
Experimentally produced hippocampal slices associative learning also ~
Strong, high frequency stimulation Minimum stimulation
1 + burst of 4 4-7 Hz
• Theta HC: Arousal & REM ~
Pattern Of Stimulation
LTP: Molecular Mechanisms
Presynaptic & Postsynaptic changes HC ---> Glutamate
excitatory 2 postsynaptic receptor subtypes
AMPA ---> Na+ NMDA ---> Ca++
Glu ligand for both ~
NMDA Receptor
N-methyl-D-aspartate Glu binding opens channel?
required, but not sufficient Membrane must be depolarized
before Glu binds ~
Single Action Potential
Glu ---> AMPA depolarization
Glu ---> NMDA does not open Mg++ blocks channel no Ca++ into postsynaptic cell
Followed by more APs ~
Activation of NMDA-R
Ca++ channel chemically-gated voltage-gated
Mg++ blocks channel Ca++ influx --->post-synaptic changes
strengthens synapse ~
LTP: Postsynaptic Changes
Receptor synthesis More synapses Shape of dendritic spines Nitric Oxide synthesis ~
Nitric Oxide - NO
Retrograde messenger Hi conc. ---> poisonous gas
Hi lipid solubility storage?
Synthesis on demand Ca++ ---> NO synthase ---> NO
Increases NT synthesis in presynaptic neuron more released during AP ~
Cerebellum Motor functions
Coordination of movements Regulation of posture
Indirect control Adjust outputs of descending tracts
Also nonmotor functions memory/language ~
The Cerebellum & Long-term Depression
Cerebellum: Anatomy
Folia & lobules analogous to sulci & gyri
Vermis - along midline output ---> ventromedial pathway
Hemispheres output ---> lateral pathway
Deep cerebellar nuclei fastigial, interposed, & dentate Major output structures ~
Cerebellum
Programs ballistic movements feed-forward control
no feedback during execution direction, force, & timing long term modification of circuits
Motor learning shift from conscious ---> unconscious ~
Cerebellum
Acts as comparator for movements compares intended to actual
performance Correction of ongoing movements
internal & external feedback deviations from intended movement ~
Cerebellum: 3 layered cortex
Molecular layer parallel fibers axons of granule cells
runs parallel to long axis of folium Purkinge cell layer
large somas axons to underlying white matter
perpendicular to main axis of folium ~
Cerebellum: 3 layered cortex
Purkinge cell layer large somas axons to underlying
white matter perpendicular to
main axis of folium ~
Cerebellum: 3 layered cortex
Granular layerinnermost layer
small, densely packed granule cells > # neurons in cerebral cortex ~
Cerebellum: & Motor Learning
Purkinje cells only output from cerebellar cortex inhibit deep cerebellar nuclei
Input to Purkinje cells Mossy fibers via parallel fibers
from spinal cord & brainstem nuclei climbing fibers
cerebral cortex & spinal cord
via inferior olivary nucleus ~
Cerebellum: & Motor Learning
1 Purkinje cell synapses.. 1 each with 200,000 parallel fibers Many with 1 climbing fiber
strong synaptic connections Climbing fibers effects of mossy fibers
transient ~
Cerebellum: & Motor Learning
Long-term depression (LTD) requires concurrent activity climbing & parallel fibers active together in activity of specific Purkinje cells
Climbing fibers may carry error signals corrections ---> parallel fiberinfluence
input specificity only affects active synapses of a parallel fiber ~
LTD Mechanisms
*Requires concurrent activity Climbing fiber
1. Ca++ *influx - voltage-gated Parallel fibers activate
2. AMPA - Na+ influx
3. mGLUR1 AMPA desensitized
Na+ influx ~
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