Homeostatic synaptic scaling is a process thought to stabilize the activity of neural circuits in response to experience-dependent perturbations, and it involves global changes in excitatory synaptic weights onto a neuron. However, there is recent in vitro evidence for the existence of local or synapse-specific forms of homeostatic synaptic plasticity that are mechanistically distinct from synaptic scaling. The occurrence of these local forms of homeostatic synaptic plasticity has not been explored in vivo. We have recently developed a system we can use to probe changes in quantal amplitude at targeted synaptic subsets, and we are using this system to determine whether convergent synaptic subsets are affected differentially by experience-dependent homeostatic plasticity mechanisms. Our system entails an optogenetic means of evoking desynchronized vesicle release selectively from LGN thalamocortical (TC) synapses or lamina-specific intracortical (IC) synapses of L4 neurons in acutely prepared brain slices of V1. Preliminary data reveals that following 4 days of monocular deprivation there is a significant potentiation in evoked TC event amplitude, consistent with the induction of homeostatic synaptic plasticity at TC inputs. To determine whether this observed potentiation is occurring as a global L4 or local TC homeostatic synaptic modification, we will compare changes in quantal properties at TC synapses with those evoked from L4 IC synapses obtained during equivalent periods of deprivation. Furthermore, we will locally disrupt GluR2 or GluR1 C-tail dependent AMPAR trafficking to determine whether the mechanisms of synaptic potentiation at TC and IC synapses are distinct. We also plan to determine whether the trends we observe are limited to L4 star pyramidal neurons or whether they are also expressed in local FS interneuron populations. Finally, we propose to develop a system utilizing Ca2+ imaging in cortical slices for assessing network-level changes associated with observed experience-dependent homeostatic synaptic plasticity mechanisms. These combined experiments will provide novel information regarding in vivo homeostasis of TC, IC and inhibitory circuitry in response to experience perturbation.
Homeostatic synaptic plasticity is thought to play an important role in maintaining normal activity following changes in neural networks. However, there is very little research that has shown how homeostatic synaptic plasticity affects brain function during altered experience. We propose the use of several new tools for testing critical properties of homeostatic synaptic plasticity in brain slices taken from visually deprived animals.
|Miska, Nathaniel J; Richter, Leonidas Ma; Cary, Brian A et al. (2018) Sensory experience inversely regulates feedforward and feedback excitation-inhibition ratio in rodent visual cortex. Elife 7:|