Dynamic gain adjustments in descending corticofugal outputs from auditory cortex compensate for cochlear nerve synaptic damage

Abstract

Layer 5 (L5) cortical projection neurons innervate far-ranging brain areas to coordinate integrative sensory processing and adaptive behaviors. Here, we characterize a compensatory plasticity in L5 auditory cortex (ACtx) projection neurons with axons that innervate the inferior colliculus (IC), thalamus, lateral amygdala and striatum. We used widefield calcium imaging to monitor daily changes in sound processing from the dense plexus of corticocollicular (CCol) axon terminals in awake adult mice. CCol sound level growth functions were stable in control conditions but showed bi-phasic gain changes following damage to cochlear afferent synapses. Auditory nerve and CCol growth functions were sharply reduced hours after cochlear synaptopathy, but CCol response gain rebounded above baseline levels by the following day and remained elevated for 2 weeks despite a persistent reduction in auditory nerve input. Sustained potentiation of excitatory ACtx projection neurons that innervate multiple limbic and subcortical auditory centers may underlie hyperexcitability and aberrant functional coupling of distributed brain networks in tinnitus.

Cochlear neural degeneration disrupts hearing in background noise by increasing auditory cortex internal noise

“…Although evidently true, this explanation fails to highlight an active role for increased neural gain in the ACtx that effectively amplifies cortical sound processing downstream of the subcortical ABR generators (Chambers et al, 2016a). In the adult ACtx, homeostatic plasticity processes in excitatory pyramidal neurons reflect a combination of increased intrinsic excitability, disinhibition by downregulation of postsynaptic GABA receptors, and sensitization by upregulation of postsynaptic AMPA receptors and AMPA-mediated synaptic currents (Asokan et al, 2018;Balaram et al, 2019;Resnik and Polley, 2017;Teichert et al, 2017;Yang et al, 2011Yang et al, , 2012. Changes in ACtx inhibitory neurons have welldefined roles in experience-dependent development and adult learning but have never been directly studied in the context of central gain regulation in adult peripheral injury models (Abs et al, 2018;D'amour and Froemke, 2015;Kuchibhotla et al, 2017;Letzkus et al, 2011;Sarro et al, 2015;Takesian et al, 2012Takesian et al, , 2018.…”

“…But, in compensating for the loss of bottom-up afferent input, central gain processes often over-shoot the mark, making central auditory neurons hypersensitive, disinhibited, hyperactive, and hypercorrelated (Eggermont, 2017). When the damage protocols are selective to the afferent pathway and do not disrupt pre-neural sound transduction, the expression of excess central gain begins earlier and is expressed more robustly overall at the level of the ACtx than at subcortical stations (Asokan et al, 2018;Balaram et al, 2019;Chambers et al, 2016aChambers et al, , 2016bQiu et al, 2000;Resnik and Polley, 2017).…”

Behavioral Approaches to Study Top-Down Influences on Active Listening

“…In this example and in other types of predictive listening, corticofugal neurons could be the nexus between long-range signals carrying predictive cues and subcortical circuits that process low-level sound features. This hypothesis and others like it could be tested in head-fixed studies of genetically tractable animal models, such as mice, which offer unique advantages over other model systems and freely moving preparations for performing targeted recordings and manipulations of specific types of auditory corticofugal neurons (Bajo et al, 2010;Xiong et al, 2015;Asokan et al, 2017;Guo et al, 2017;Williamson and Polley, 2019; FIGURE 1 | A proposed role for descending projections in predictive listening tasks. (A) A basic consonant recognition task is easier in the presence of visual speech cues (e.g., mouth movements).…”