Some circuitsthose that function primarily as relaysprobably do not show prominent plasticity. and understanding plasticity in the cellular level in auditory brainstem and midbrain. These studies possess pointed to refinements in synaptic inhibition as a major end result of plasticity. At a superficial level, one might be rather surprised that classical synaptic plasticity is definitely a prominent house of the early levels of auditory processing, based on the assumption that synaptic properties must be invariant in order to support right understanding of acoustic features. Computations that require exact preservation of maps, whether in the brainstem or the cortex, is probably not well served by time-dependent changes in synaptic function. For example, the sub-millisecond interaural time variations that underlie the detection of a sounds location in space could be jeopardized by weakening or conditioning of synapses in different environments. On the other hand, neural representation and discrimination of sound space and rate of recurrence may switch with development in head size or in structural features of ear canals (Sanes and Walsh, 1997; Werner BQR695 and Gray, 1997). Moreover, convergence of auditory maps with additional sensory modalities requires a mechanism for tuning the precision of overlap, as offers been shown in the midbrain of owls (Keuroghlian and Knudsen, 2007). The generality of hearing loss in humans has motivated a wealth of studies of its neural effects in animal models, and the results offer clear evidence for plasticity at every level of the central auditory system (Takesian et al., 2009). Furthermore, studies of auditory deficits or alteration in multisensory representations spotlight a key role for plasticity of inhibitory neurons that control the magnitude, distribution, and temporal features of acoustic responses in the brain. Here, we review work on plasticity mechanisms and function in the auditory brainstem and midbrain, focusing on areas where plasticity of inhibitory signaling may contribute to developmental circuit refinement and multimodal integration. 2. Circuits and inhibitory neurons subserving auditory processing The hallmarks of the auditory pathways are parallel streams of information, their convergence at multiple levels of the neuraxis, and prominent descending inputs at all levels (Smith and Spirou, 2001). Auditory nerve fibers, each made up of limited information about sound frequency and intensity, branch in the cochlear nucleus to contact diverse cell types that establish particular processing pathways. Six main way stations of processing are found, including the cochlear nuclei, the superior olivary nuclei, the lateral lemniscal nuclei, the substandard colliculus, thalamus and cortex (fig 1). Diverse subtypes of inhibitory neurons are found at every level. The roles of these cells are just beginning to be appreciated as newer methods for identification and recording from such cells are developed. Open in a separate windows Fig. 1 Outline of the 5 major parts of the centeral auditory pathway. Adapted with permission from an image by S Blatrix, from “Promenade round the cochlea” http://www.cochlea.org EDU website by R Pujol et al., INSERM and University Montpellier. Beyond the level of description of cell types and activity dependence of synaptic function, understanding the function of plasticity at inhibitory neurons will be a major challenge. Three interesting aspects of inhibition in the auditory system add to BQR695 this challenge. First, inhibitory neurons, at least in the brainstem, are both local interneurons and projection cells. For example, auditory nerve fibers synapse upon glycinergic D-stellate cells of the ventral cochlear nucleus, which in turn provide inhibition both to ipsi-and contralateral cochlear nuclei, and contact cells of quite diverse computational function. D-stellate cells mediate broadband inhibition within the dorsal cochlear nucleus (DCN), a nucleus involved in localizing sound elevation, and also mediate contralateral inhibition of ventral cochlear nuclear T-stellate cells, which are involved BQR695 in pitch coding (Doucet et al., 2009; Needham and Paolini, 2007). As another example, glycinergic principal cells of the medial nucleus of the trapezoid body (MNTB) project to regions involved in binaural processing based on both interaural timing and intensity (Tollin, 2003). As a result, plasticity of neurons in these examples would have quite diverse effects. Second, inhibition in the auditory system is usually mediated by glycine, GABA, and, not uncommonly, by co-release of both transmitters (Lu et al., 2008). Thus, receptor regulation associated with inhibitory plasticity in a.Summary and Conclusions Synaptic plasticity is an important feature at subsets of synapses made onto and by inhibitory neurons of the lower auditory pathways. years, there has been an emerging interest in identifying and understanding plasticity at the cellular level in auditory brainstem and midbrain. These studies have pointed to refinements in synaptic inhibition as a major end result of plasticity. At a superficial level, one might be rather surprised that classical synaptic plasticity is usually a prominent house of the early levels of auditory processing, based on the assumption that synaptic properties must be invariant in order to support correct belief of acoustic features. Computations that require precise preservation of maps, whether in the brainstem or the cortex, might not be well served by time-dependent changes in synaptic function. For example, the sub-millisecond interaural time differences that underlie the detection of a sounds location in space could be compromised by weakening or strengthening of synapses in different environments. On the other hand, neural representation and discrimination of sound space and frequency may switch with development in head size or in structural features of ear canals (Sanes and Walsh, 1997; Werner and Gray, 1997). Moreover, convergence of auditory maps with other sensory modalities requires a mechanism for tuning the precision of overlap, as has been shown in the midbrain of owls (Keuroghlian and Knudsen, 2007). The generality of hearing loss in humans has motivated a wealth of studies of its neural effects in animal models, and the results offer clear evidence for plasticity at every level of the central auditory system (Takesian et al., 2009). Furthermore, studies of auditory deficits or alteration in multisensory representations spotlight a key role for plasticity of inhibitory neurons that control the magnitude, distribution, and temporal features of acoustic responses in the brain. Here, we review work on plasticity mechanisms and function in the auditory brainstem and midbrain, focusing on areas where plasticity of inhibitory signaling may contribute to developmental circuit refinement and multimodal integration. 2. Circuits and inhibitory neurons subserving auditory processing The BQR695 hallmarks of the auditory pathways are parallel streams of information, their convergence at multiple levels of the neuraxis, and prominent descending inputs at all levels (Smith and Spirou, 2001). Auditory nerve fibers, each made up of limited information about sound frequency and intensity, branch in the cochlear nucleus to contact diverse cell types that establish particular processing pathways. Six main way stations of processing are found, including the cochlear nuclei, the superior olivary nuclei, the lateral lemniscal nuclei, the substandard colliculus, thalamus and cortex (fig 1). Diverse subtypes of inhibitory neurons are found at every level. The functions of these cells are just beginning to be appreciated as newer methods for identification and recording from such cells are developed. Open in a separate windows Fig. 1 Outline of the 5 NFBD1 major parts of the centeral auditory pathway. Adapted with permission from an image by S Blatrix, from “Promenade round the cochlea” http://www.cochlea.org EDU website by R Pujol et al., INSERM and University or college Montpellier. Beyond the level of description of cell types and activity dependence of synaptic function, understanding the function of plasticity at inhibitory neurons will be a major challenge. Three interesting aspects of inhibition in the auditory system add to this challenge. First, inhibitory neurons, at least in the brainstem, are both local interneurons and projection cells. For example, auditory nerve fibers synapse upon glycinergic D-stellate cells of the ventral cochlear nucleus,.