Neuronal subtype identity in the rat auditory brainstem as defined by molecular profile and axonal projection.

The nuclei of the auditory brainstem harbor a diversity of neuronal cell types and are interconnected by excitatory as well as inhibitory ascending, descending, and commissural pathways. Classically, neurons have been characterized by size and shape of their cell body and by the geometry of their dendrites. Our study is based on the use of axonal tracers in combination with immunocytochemistry to identify and distinguish neuronal subtypes by their molecular signature in dorsal and ventral cochlear nucleus, lateral superior olive, medial superior olive, medial nucleus of the trapezoid body, and inferior colliculus of the adult rat. The presumed neurotransmitters glutamate, glycine, and GABA were used alongside the calcium-binding proteins parvalbumin, calretinin, and calbindin-D28k as molecular markers. Our data provide distinct extensions to previous characterizations of neuronal subtypes and reveal regularities and differences across auditory brainstem nuclei that are discussed for their functional implications.

Immediate early gene expression invoked by electrical intracochlear stimulation in some but not all types of neurons in the rat auditory brainstem.

Specific patterns of sensory activity may induce plastic remodeling of neurons and the communication network they form in the adult mammalian brain. Among the indicators for the initiation of neuronal remodeling is the expression of immediate early genes (IEGs). The IEGs c-fos and egr-1 encode transcription factors. Following spectrally and temporally precisely defined unilateral electrical intracochlear stimulation (EIS) that corresponded in strength to physiological acoustic stimuli and lasted for 2 h under anesthesia, we characterized those neuronal cell types in ventral (VCN) and dorsal cochlear nucleus (DCN), lateral superior olive (LSO) and central nucleus of the inferior colliculus (CIC) of the rat brain that expressed IEGs. We found that EIS affected only specific types of neurons. Whereas sub-populations of glutamatergic and glycinergic cells responded in all four regions, GABAergic neurons failed to do so except in DCN. Combining immunocytochemistry with axonal tracing, neurons participating in major ascending pathways, commissural cells of VCN and certain types of neurons of the descending auditory system were seen to respond to EIS with IEG expression. By contrast, principal LSO cells projecting to the contralateral CIC as well as collicular efferents of the DCN did not. In total, less than 50% of the identified neurons turned up expression of the IEGs studied. The pattern of IEG expression caused by unilateral EIS led us to suggest that dominant sensory activity may quickly initiate a facilitation of central pathways serving the active ear at the expense of those serving the unstimulated ear.

Specific plasticity responses to unilaterally decreased or increased hearing intensity in the adult cochlear nucleus and beyond.

Variations of sensory activation in strength and pattern are known to affect structure and function of the mammalian brain. Whereas such malleability is readily granted to forebrain structures at early developmental stages, acceptance of experience-dependent structural plasticity has been slow for the adult brainstem. Over the past years we have identified consequences of cochlear ablation, noise trauma, or electrical intracochlear stimulation on neurons and circuitry of the auditory brainstem of the adult rat. We found that loss of sensory activation as well as a substitution for it entail specific molecular, ultrastructural, and morphological changes to central auditory neurons. Here, we make a first attempt to compare these different patterns of central remodeling. We tentatively suggest that after hearing loss or intracochlear stimulation responses of the central neural network in the adult brainstem suit the concept of functional adaptation.