Permanent Deafness. A Perfect Storm in Brain Sensory Cortex

Abstract

In order to build the perceptual scene, the brains of mammals have developed neural circuits, specialized in analyzing and mixing different sources of sensory information. This ability requires a dynamic multimodal interchange of information along all stations of the sensory pathways from the brainstem to the cerebral cortex. When one sensory system fails, the brain cortex reorganizes its neural networks to preserve intermodal processing, what is known as cross-modal plasticity. In deafened ferrets, “de novo” emerging somatosensory responses have been shown by single unit recording in the auditory cortex (AC), undoubtedly demonstrating a multimodal sensory conversion in the brain cortex after sensory deprivation (Allman et al., 2009). Since receptive fields involve inhibitory GABA interactions, as demonstrated by iontophoresis (Tremere et al., 2001), such sensory conversion may reflect imbalanced cortical multimodal neurotransmission. Our results in a model of bilateral long-term deafness indicate that hearing deprivation induces an altered functional intermodal interaction which involves increased activation of the visual cortex (VC). Also, in humans, VC overactivation after permanent and long-term deafness has been demonstrated using visual evoked potentials (Neville et al., 1983). It is known that cross-modal balance for sensory processing between primary cortices is the result of a combination of thalamic drivers’ activation, horizontal polymodal connections, and intrinsic microcircuit elaboration of neuronal responses in the cortical columns. Data will be presented in this talk pointing out that after chronic and permanent deafness in the rat, a cross-modal reorganization is triggered by changes in inhibitory circuits. Such rebound of inhibition has been shown by increases in gene expression and immunoreactivity for GAD 65 and GAD 67 as well as by increases in parvalbumin positive (PV) fast-spiking interneurons. Overactivation of the VC in our model, as demonstrated by changes in activity-dependent early immediate expression genes c-Fos and Arc/Arg 3.1 and VEPs recordings (Pernia et al., 2017), is generated by imbalanced horizontal interactions as indicated by restricted changes of immunocytochemical markers in layers 2/3. However, such imbalance does not equally affect both primary cortices. Because GABA interneurons specifically increase in primary AC, greater inhibition of cortical column microcircuits could be expected (fast-spiking control). Our results also indicate that two homeostatic mechanisms actively work for a dynamic compensation of the out-of-balance bimodal relationship after deafness: (1) Increases in the expression and protein synthesis of AMPA receptors in the AC (which indicates an effort to compensate changes in its thalamic drivers’ activation), and (2) the up-regulation of Arc/Arg3.1 shown by us in the VC which supports a reactive mechanism to compensate overactivation in the VC. In sum after prolonged deafness, cross-modal reorganization at long term induces the overactivation of neighboring sensory cortices (in particular VC) as a result of a dynamic compensation of the horizontal feedbacks. We have recently shown that anodal continuous current stimulation allows restricted over-activation of the AC (Colmenarez-Raga et al., 2019). A restricted stimulation with anodal currents (activation) in the AC may be able to rebalance cross-modal reaction, potentially improving cortical processing after cochlear implantation. New strategies of directional restricted neuromodulation of sensory cortices by electric fields by using the novel method of non-invasive deep brain stimulation via temporally interfering electric fields (Grossman et al., 2017) will be also discussed in this talk.