Vision Loss Shifts the Balance of Feedforward and Intracortical Circuits in Opposite Directions in Mouse Primary Auditory and Visual Cortices

Abstract

Loss of a sensory modality leads to widespread changes in synaptic function across sensory cortices, which are thought to be the basis for cross-modal adaptation. Previous studies suggest that experience-dependent cross-modal regulation of the spared sensory cortices may be mediated by changes in cortical circuits. Here, we report that loss of vision, in the form of dark exposure (DE) for 1 week, produces laminar-specific changes in excitatory and inhibitory circuits in the primary auditory cortex (A1) of adult mice to promote feedforward (FF) processing and also strengthens intracortical inputs to primary visual cortex (V1). Specifically, DE potentiated FF excitatory synapses from layer 4 (L4) to L2/3 in A1 and recurrent excitatory inputs in A1-L4 in parallel with a reduction in the strength of lateral intracortical excitatory inputs to A1-L2/3. This suggests a shift in processing in favor of FF information at the expense of intracortical processing. Vision loss also strengthened inhibitory synaptic function in L4 and L2/3 of A1, but via laminar specific mechanisms. In A1-L4, DE specifically potentiated the evoked synaptic transmission from parvalbumin-positive inhibitory interneurons to principal neurons without changes in spontaneous miniature IPSCs (mIPSCs). In contrast, DE specifically increased the frequency of mIPSCs in A1-L2/3. In V1, FF excitatory inputs were unaltered by DE, whereas lateral intracortical connections in L2/3 were strengthened, suggesting a shift toward intracortical processing. Our results suggest that loss of vision produces distinct circuit changes in the spared and deprived sensory cortices to shift between FF and intracortical processing to allow adaptation.

Cross-Modality Sharpening of Visual Cortical Processing through Layer-1-Mediated Inhibition and Disinhibition

“…As such, barely detectable images of predators in a dim environment may be better perceived by rodents when there are sounds coincidentally associated with the threats. Arising from the current results are several intriguing questions: how this top-down circuit is formed during development; whether it is hardwired or if it can be shaped by visual or auditory experience (Petrus et al, 2014; Petrus et al, 2015). Studying the A1-V1 circuit in the developing brain of both naïve and experientially manipulated animals will thus be an exciting future research direction.…”

Experience-Dependent and Differential Regulation of Local and Long-Range Excitatory Neocortical Circuits by Postsynaptic Mef2c

“…To test this possibility, we evoked EPSCs onto WT and MEF2C KO neuron pairs with extracellular electrical stimulation of adjacent L2/3 through which horizontally projecting axons from both local and long-range intercortical pathways pass (Petreanu et al, 2007; Petrus et al, 2015) (Fig. 1E 1 ).…”

“…To further test this hypothesis, we measured L4-evoked AMPAR-EPSCs onto WT and MEF2C KO L2/3 neurons in strontium (Sr +2 ). Sr +2 asynchronizes glutamate release and allows the resolution of quantal synaptic events (Petrus et al, 2015). Consistent with an effect on synapse number, Mef2c deletion decreased the frequency (~40%), but not amplitude of L4-evoked quantal events (Fig.…”

Visual experience sculpts whole-cortex spontaneous infraslow activity patterns through an Arc-dependent mechanism

“…In addition to anatomic change, cross-modal plasticity also involves homeostatic plasticity mechanisms that drive alterations in synaptic strength. Enhanced evoked responses to auditory and tactile stimuli have been reported in mice within days of deprivation (50). Congenitally blind humans exhibit widespread changes in ISA correlation in multiple networks (30,31), suggesting that cross-modal plasticity involves altered spontaneous activity relationships over long distances.…”

“…Although these findings are currently debated, it is clear that loss of a single sensory modality alters anatomical and functional relationships between distinct brain systems (30,31,(48)(49)(50)(51). Cross-modal plasticity has been demonstrated by physiologic and molecular assays in humans (30,31), cats (52), rodents (50), and even Caenorhabditis elegans (53), which suggests it is a generalizable property of the nervous system. We suggest that enhanced internetwork correlation of ISA observed after BD (among visual, cingulate, and motor networks) may be a signature of cross-modal plasticity.…”