From behavioral context to receptors: serotonergic modulatory pathways in the IC

Abstract

In addition to ascending, descending, and lateral auditory projections, inputs extrinsic to the auditory system also influence neural processing in the inferior colliculus (IC). These types of inputs often have an important role in signaling salient factors such as behavioral context or internal state. One route for such extrinsic information is through centralized neuromodulatory networks like the serotonergic system. Serotonergic inputs to the IC originate from centralized raphe nuclei, release serotonin in the IC, and activate serotonin receptors expressed by auditory neurons. Different types of serotonin receptors act as parallel pathways regulating specific features of circuitry within the IC. This results from variation in subcellular localizations and effector pathways of different receptors, which consequently influence auditory responses in distinct ways. Serotonin receptors may regulate GABAergic inhibition, influence response gain, alter spike timing, or have effects that are dependent on the level of activity. Serotonin receptor types additionally interact in nonadditive ways to produce distinct combinatorial effects. This array of effects of serotonin is likely to depend on behavioral context, since the levels of serotonin in the IC transiently increase during behavioral events including stressful situations and social interaction. These studies support a broad model of serotonin receptors as a link between behavioral context and reconfiguration of circuitry in the IC, and the resulting possibility that plasticity at the level of specific receptor types could alter the relationship between context and circuit function.

Socially induced serotonergic fluctuations in the male auditory midbrain correlate with female behavior during courtship

“…In multiple brain areas, serotonergic fluctuations reflect shifts in social context (Hall et al 2011;Mas et al 1995;Nakazato 2013;Watt et al 2007). Serotonin is also a strong modulator of sensory responses to incoming social stimuli (Deemyad et al 2013;Hurley and Sullivan 2012). The social responsiveness of the serotonergic system thus has a potentially important role in sensory processing during conspecific interaction.…”

Neuromodulation of early electrosensory processing in gymnotiform weakly electric fish

“…This is, for example, the case for the midbrain TSd. Both cholinergic and serotonergic inputs are likely to have qualitatively different effects on different cell types in the TSd based on studies performed in other midbrain structures (Hurley et al, 2004;Hurley and Sullivan, 2012). Knowledge of the behavioural contexts and stimulus features that reliably activate serotonergic and cholinergic inputs to the ELL as well as other electrosensory structures will be essential for developing a functional theory of neuromodulation of sensory processing.…”

“…Significant progress has been made in unravelling the relationships between the effects of neuromodulators at the cellular and at the systems level, i.e. the processing of sensory stimuli and its consequences for behaviour (for reviews, see Birmingham and Tauck, 2003;Edeline, 2012;Hurley et al, 2004;Hurley and Sullivan, 2012;Witkovsky, 2004). For example, at the single-cell level, neuromodulators have been implicated in facilitation of evoked responses, increases in signal-to-noise ratio, and improved functional properties of sensory neurons in the visual, auditory and somatosensory systems (for reviews, see Edeline, 2012;Hurley et al, 2004;Hurley and Sullivan, 2012).…”

“…the processing of sensory stimuli and its consequences for behaviour (for reviews, see Birmingham and Tauck, 2003;Edeline, 2012;Hurley et al, 2004;Hurley and Sullivan, 2012;Witkovsky, 2004). For example, at the single-cell level, neuromodulators have been implicated in facilitation of evoked responses, increases in signal-to-noise ratio, and improved functional properties of sensory neurons in the visual, auditory and somatosensory systems (for reviews, see Edeline, 2012;Hurley et al, 2004;Hurley and Sullivan, 2012). In invertebrates, neuromodulators have been shown to enhance sensitivity of, and odour discrimination by, ensembles of olfactory neurons (Dacks et al, 2009) and to modulate spike timing precision in mechanosensory neurons (Billimoria et al, 2006).…”

Involvement of the Serotonin Transporter Gene in Accurate Subcortical Speech Encoding

“…In particular, animal studies have demonstrated that serotonin alters multiple aspects of the neural response to sound. Not only does it change the number of spikes evoked by auditory stimuli Pollak, 1999, 2001), but also the latency and precision of initial spikes and the timing of spike trains and therefore all response properties contributing to the encoding of sensory stimuli (Hurley and Pollak, 2005). As the serotonin transporter [5-HT transporter (5-HTT)] is considered to be crucial for the regulation of serotonin availability and a common functional polymorphism has been identified in the serotonin transporter gene (SLC6A4; Heils et al, 1996), we hypothesized that it might be implicated in subcortical auditory processing.…”