Visual Deprivation Selectively Reduces Thalamic Reticular Nucleus-Mediated Inhibition of the Auditory Thalamus in Adults

Abstract

Sensory loss leads to widespread cross-modal plasticity across brain areas to allow the remaining senses to guide behavior. While multimodal sensory interactions are often attributed to higher-order sensory areas, cross-modal plasticity has been observed at the level of synaptic changes even across primary sensory cortices. In particular, vision loss leads to widespread circuit adaptation in the primary auditory cortex (A1) even in adults. Here we report using mice of both sexes in which cross-modal plasticity occurs even earlier in the sensory-processing pathway at the level of the thalamus in a modality-selective manner. A week of visual deprivation reduced inhibitory synaptic transmission from the thalamic reticular nucleus (TRN) to the primary auditory thalamus (MGBv) without changes to the primary visual thalamus (dLGN). The plasticity of TRN inhibition to MGBv was observed as a reduction in postsynaptic gain and short-term depression. There was no observable plasticity of the cortical feedback excitatory synaptic transmission from the primary visual cortex to dLGN or TRN and A1 to MGBv, which suggests that the visual deprivation-induced plasticity occurs predominantly at the level of thalamic inhibition. We provide evidence that visual deprivation-induced change in the short-term depression of TRN inhibition to MGBv involves endocannabinoid CB1 receptors. TRN inhibition is considered critical for sensory gating, selective attention, and multimodal performances; hence, its plasticity has implications for sensory processing. Our results suggest that selective disinhibition and altered short-term dynamics of TRN inhibition in the spared thalamic nucleus support cross-modal plasticity in the adult brain.SIGNIFICANCE STATEMENTLosing vision triggers adaptation of the brain to enhance the processing of the remaining senses, which can be observed as better auditory performance in blind subjects. We previously found that depriving vision of adult rodents produces widespread circuit reorganization in the primary auditory cortex and enhances auditory processing at a neural level. Here we report that visual deprivation-induced plasticity in adults occurs much earlier in the auditory pathway, at the level of thalamic inhibition. Sensory processing is largely gated at the level of the thalamus via strong cortical feedback inhibition mediated through the thalamic reticular nucleus (TRN). We found that TRN inhibition of the auditory thalamus is selectively reduced by visual deprivation, thus playing a role in adult cross-modal plasticity.

Dark exposure reduces high-frequency hearing loss in C57BL/6J mice

“…Indeed, training on auditory temporal discrimination tasks can also improve spectral tuning (28), suggesting that mechanisms engaged by training are affecting general sound processing. Given that DE has an effect on thalamic (14), thalamocortical (10), and intracortical (11-13) auditory circuits we expect that performance in a variety of auditory tasks is improved. Our data show an enhancement of the performance at high frequencies in C57BL/6J mice.…”

“…After DE, ascending and recurrent intracortical circuits change synaptic strength (11)(12)(13), and refine their connections, leading to a more efficient information transmission (12). In addition to changes on the cortical and thalamocortical level, DE reduces inhibition from the thalamic reticular nucleus to the auditory thalamus, enhancing the ascending transmission of sound information through the thalamus (14). DE could also have effects on spectral contrast tuning sensitivity (30).…”

“…Several circuitlevel plasticity changes have been observed in adult mice with temporary visual deprivation (dark exposure, DE). DE in adult mice has profound effects on the primary auditory cortex, such as strengthening of thalamocortical synapses (10), refinement of excitatory and inhibitory intracortical circuits (11)(12)(13), and selective reduction of thalamic-reticular nucleus-mediated inhibition of the auditory thalamus (14). These circuit changes correlate with changes in the sound-evoked responses, such as reduced thresholds, increased gain, increased frequency selectivity (10), and decorrelation of spatiotemporal population responses (15), which together should lead to increased coding fidelity.…”

Metaplasticity framework for cross-modal synaptic plasticity in adults

“…Sensory loss produces compensatory plasticity in the spared sensory cortices and cross-modal recruitment plasticity in the deprive sensory cortex. Lower panels show compilation of synaptic plasticity data from adult mice after vision loss (Petrus et al, 2014(Petrus et al, , 2015Whitt et al, 2022). (Lower right panel) In the deprived primary visual cortex (V1), there is no plasticity of the feedforward (thalamocortical inputs to L4 and L4-L2/3) or the thalamic circuit, but lateral inputs to L2/3 potentiate.…”

“…For cross-modal plasticity in A1, the evidence suggests a central mechanism that may amplify auditory activity. This may be achieved by a targeted reduction in thalamic inhibition (Whitt et al, 2022). Specifically, depriving vision of adult mice caused a selective reduction of thalamic reticular nucleus (TRN) inhibition to the auditory thalamus [ventral portion of medial geniculate body (MGBv)] but not to the visual thalamus [dorsal lateral geniculate nucleus (dLGN)] (Figure 1).…”