The serotonin releaser fenfluramine alters the auditory responses of inferior colliculus neurons

Abstract

Local direct application of the neuromodulator serotonin strongly influences auditory response properties of neurons in the inferior colliculus (IC), but endogenous stores of serotonin may be released in a distinct spatial or temporal pattern. To explore this issue, the serotonin releaser fenfluramine was iontophoretically applied to extracellularly recorded neurons in the IC of the Mexican free-tailed bat (Tadarida brasiliensis). Fenfluramine mimicked the effects of serotonin on spike count and first spike latency in most neurons, and its effects could be blocked by co-application of serotonin receptor antagonists, consistent with fenfluramine-evoked serotonin release. Responses to fenfluramine did not vary during single applications or across multiple applications, suggesting that fenfluramine did not deplete serotonin stores. A predicted gradient in the effects of fenfluramine with serotonin fiber density was not observed, but neurons with fenfluramine-evoked increases in latency occurred at relatively greater recording depths compared to other neurons with similar characteristic frequencies. These findings support the conclusion that there may be spatial differences in the effects of exogenous and endogenous sources of serotonin, but that other factors such as the identities and locations of serotonin receptors are also likely to play a role in determining the dynamics of serotonergic effects.

Activation of the serotonin 1A receptor alters the temporal characteristics of auditory responses in the inferior colliculus

“…The current study provides evidence that long-latency neurons are also especially sensitive to serotonergic modulation. A caveat to this conclusion is that it is possible that the activation of 5-HT 1A receptors by endogenous serotonin release could have prevented the full range of effects of the iontophoresed agonist from being observed (Hall and Hurley, 2007). An alternative interpretation of the data is therefore that the 5-HT 1A receptors of shorter-latency neurons are already occupied by endogenously released serotonin.…”

“…Variation in all three of these neural characteristics has been explored in the Mexican freetailed bat (Tadarida brasiliensis; Klug et al, 2002;Hurley and Pollak, 2005b;Hall and Hurley, 2007). This species was used in the current study for this and several additional reasons.…”

Transient gain adjustment in the inferior colliculus is serotonin- and calcium-dependent

“…Recent studies that pharmacologically-controlled serotonergic receptor activation and serotonin release in the IC have also demonstrated a role for serotonin in auditory coding (Hurley 2006; Hurley 2007; Hall and Hurley 2007; Hurley et al 2008). Thus, endogenous serotonin is present in the intact IC, and is likely to modulate acoustic processing.…”

“…Frequency tuning properties can be altered either by stimulation of ascending cholinergic afferents, or focal application of serotonin (Ji et al 2001, Ma and Suga 2003; Hurley and Pollak 1999, 2001; Hurley 2006; Hurley 2007; Hurley 2008). Indeed, activation of serotonin can have a variety of effects on the timing and magnitude of frequency tuning, due to the diversity of receptor subtypes present in the IC (Hall and Hurley 2007; Hurley 2007; Hurley et al 2008). The recruitment of postsynaptic calcium currents in IC neurons may also support response enhancement.…”

Activation of serotonin 3 receptors changes in vivo auditory responses in the mouse inferior colliculus

“…Exogenously applied and endogenously released serotonin both have a range of effects on IC auditory responses including the contraction or expansion of frequency receptive fields and the alteration of temporal response properties (Hurley and Pollak 1999, 2001; Hall and Hurley 2007). Similar to other regions of the brain, variation in the expression of different types of serotonin receptors contributes to these effects.…”