Transcript pdf
How do we know that functional synapses are eliminated during maturation? A: Measurement of PSP amplitude after presynaptic stimulation in developing vs. mature synapses The postsynaptic potential generated by multiple afferents is additive Fewer inputs generate less PSP in mature synapses Blocking synaptic activity with TTX prevents synapse elimination Converse experiment: excess stimulation precocious synapse elimination Rat soleus muscle (leg)/ sciatic nerve Greater distance between nerve terminals: less elimination > 2-3 mm: both synapses may survive 1-2 mm: one synapse will be removed With dual innervation, strong synaptic activity of the 1st depresses activation of 2nd synapse 2 motor nerve roots: less current Does synaptic depression lead to synapse elimination? Yes: the AChR blockade experiment Pharmacological blockade Normal development Loss of AChRs precedes synapse elimination (live imaging) reduced AChRs Red/yellow: Rhodamine-bungarotoxin Protein kinases A & C (PKA/PKC) mediate activity-dependent synaptic loss Postsynaptic Ca2+ depresses synaptic activity, unless presynaptic cell is stimulated caged Ca2+ in muscle: UV-stimulated During development, synapses can be rearranged on target cells Mammalian retinogeniculocortical (visual) pathway for binocular vision In the visual cortex layer IV, LGN terminals are initially mixed, then resolve into columns In the LGN, layers form to segregate RGC inputs, then ocular dominance columns are generated in cortex Tracing the cat visual pathway during the first few months Excessive innervation in the cortex is removed between P22-P92 Covering one eye from 2 wks – 22 mo leads to expanded eyespecific cortical domains in layer IV Control Monoculardeprived Cortical domains= Ocular dominance columns Single-neuron recordings in vivo: the majority of neurons are binocular (respond to input from both eyes) Extracellular electrode Layer IV neurons: monocular Layers I-III, V-VI: neurons respond to both eyes If one eye is closed throughout life, it will lose its synaptic connectivity No visual input during development does not eradicate ocular dominance columns or response to visual stimuli # responsive neurons is much lower than non-deprived controls Deflection of one eye strongly suppresses binocular innervation *timing of activation must be critical to maintain connectivity Strabismus also changes intrinsic local cortical projections Retrograde dye labeling: in strabismic cortex, local projections to other layers are confined to monocular columns Uncorrelated inputs segregate • Synchronous stimulation of optic nerves blurs segregation • Asynchronous stimulation of optic nerves sharpens segregation In development of the visual pathway, synaptic refinement occurs first in the LGN, then in the cortex (IV) Before light input, RGCs begin firing in waves across retina Spontaneous waves of RGC activity are lost by P15 Only blockade of neuronal activity ablates formation of columns Donald Hebb, psychologist (1904-1985) - The Hebbian theory: synaptic strength is derived from repeated and persistent stimulation of a postsynaptic cell by a presynaptic neuron Carla Shatz, neurobiologist “Cells that fire together, wire together”: The presynaptic cell must fire first, and in turn cause the postsynaptic cell to fire Synapses are strengthened by synchronous firing on shared target