Synaptic Plasticity

Synaptic plasticity     Changes in the effectiveness (ease of signal transmission) of a synapse. Short-term changes take seconds to minutes; long-term changes take hours to days. Short periods of synaptic activation can result in facilitation. o A pair of presynaptic action potentials elicits two EPSPs. o By increasing the interval between pairs of presynaptic action potentials, potentiation can be seen to decay over time. Long term changes in signalling can cause: o Long term potentiation. o Long term depression. o Changes in synaptic transmission. Long term potentiation  Induced by a high frequency (>15Hz) stimulus.  High frequency stimulation causes an increase in post-synaptic response compared to normal.  Most experimental work has come from studies in the hippocampal formation. o Dentate gyrus and hippocampus. o Features orderly arrangement of cells and input paths. o High frequency stimulation of perforant path produces an increase in amplitude of excitatory synaptic potentials that last for hours or days.  Mechanism: o When pre-synaptic neuron is stimulated, it releases glutamate, which acts on NMDA receptors. o NMDA receptors allow influx of Ca2+, which in high concentrations, leads to activation of protein kinases (calmodulin kinase II and protein kinase C). o High [Ca2+] in post-synaptic neuron also has a feedback loop on the pre-synaptic neuron, as it enhances transmitter release.  In order for long term potentiation to occur: o Synapses must be activated at the same time that the postsynaptic cell is strongly depolarised, because NMDA receptors are voltage-gated. o Post-synaptically increased [Ca2+]. o Increased PSP. o Activation of calmodulin kinase II (CaMKII) and protein kinase C. Long term depression  Prolonged depression of synaptic transmission.  Induced by a variety of stimulation protocols including prolonged low frequency stimulation (1 – 5 stimuli/s for 5 – 15 mintues). Flow of information through neocortex  Vertical connections: o Sensory information ascends to cortex via thalamo-cortico axons. o Sensory cortex has 6 layers. o Thalamo-cortico axons terminate in layer IV (layer IV  layer II/III  layer V  layer IV). o Cortical output (to other cortical and subcortical areas) via pyramidal cells in layers V and VI.  Horizontal connections: o Serve to integrate information from neighbouring and distant regions. o Arise from layers II/III and V pyramidal cells. o Unknown what proportion of synapses originate locally, but even in layer IV, only 15 – 20% of synapses originate from thalamus. o Horizontal connectivity is important in cortical map plasticity. o Cortical based changes probably involve sprouting of dendritic spines, where synaptic connections with other neurons occur. Rat whisker system  The whisker area of the rat somatosensory cortex is arranged as a topographic map of the whiskers.  Sensory information from one whisker supplies one discrete region of the cortex.  After snipping certain whiskers, connections were made between neurons, thus providing sensory input for that region. Training  Increased use of a body part by an animal leads to an increase in the brain’s cortical representation of that body part.  In constraint-induced therapy for patients after a stroke, a patient’s: o Unaffected limb is restrained for 90% of waking day. o The impaired limb undergoes intense training for many hours each day, five days a week, for two or three weeks. Results show a change in grey matter in motor areas and hippocampus