Serotonin 1B Receptor Modulates Frequency Response Curves and Spectral Integration in the Inferior Colliculus by Reducing GABAergic Inhibition

Abstract

Hurley LM, Tracy JA, Bohorquez A. Serotonin 1B receptor modulates frequency response curves and spectral integration in the inferior colliculus by reducing GABAergic inhibition. J Neurophysiol 100: 1656 -1667, 2008. First published July 16, 2008 doi:10.1152/jn.90536.2008. The selectivity of sensory neurons for stimuli is often shaped by a balance between excitatory and inhibitory inputs, making this balance an effective target for regulation. In the inferior colliculus (IC), an auditory midbrain nucleus, the amplitude and selectivity of frequency response curves are altered by the neuromodulator serotonin, but the changes in excitatoryinhibitory balance that mediate this plasticity are not well understood. Previous findings suggest that the presynaptic 5-HT1B receptor may act to decrease the release of GABA onto IC neurons. Here, in vivo extracellular recording and iontophoresis of the selective 5-HT1B agonist CP93129 were used to characterize inhibition within and surrounding frequency response curves using two-tone protocols to indirectly measure inhibition as a decrease in spikes relative to an excitatory tone alone. The 5-HT1B agonist attenuated such two-tone spike reduction in a varied pattern among neurons, suggesting that the function of 5-HT1B modulation also varies. The hypothesis that the 5-HT1B receptor reduces inhibition was tested by comparing the effects of CP93129 and the GABA A antagonists bicuculline and gabazine in the same neurons. The effects of GABA A antagonists on spike count, tuning bandwidth, twotone ratio, and temporal response characteristics mimicked those of CP93129 across the neuron population. GABA A antagonists also blocked or reduced the facilitation of evoked responses by CP93129. These results are all consistent with the reduction of GABA A -mediated inhibition by 5-HT1B receptors in the IC, resulting in an increase in the level of evoked responses in some neurons, and a decrease in spectral selectivity in others. I N T R O D U C T I O NNeuromodulatory signals such as serotonin are broadly released in the brain in response to changes in internal state (Trulson andJacobs 1979, 1981) but transform the response properties of sensory neurons in highly specific ways (Hurley et al. 2004;Mooney et al. 1996;Xiang and Prince 2003). This specificity is achieved through the targeting of classes of neurons by a variety of receptor types that may alter intrinsic neuron properties or target presynaptic neurons and alter the release of neurotransmitter (Hoyer et al. 1994(Hoyer et al. , 2002. One consequence of these effects is that serotonin can alter the balance of different types of inputs within sensory regions. For example, serotonin may alter the balance between ascending versus descending projections (Mooney et al. 1996) or the balance between within-versus between-layer communication in the cortex (Xiang and Prince 2003).In the inferior colliculus (IC), an auditory midbrain nucleus, serotonin modifies a number of response properties, including both spectral and temporal aspects of ev...

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

“…However, the serotonergic elevations measured in this study are likely to modulate the responses to acoustic stimuli by IC neurons, which express a range of different serotonin receptor types, including receptors in the metabotropic 5-HT1 and 5-HT2 families as well as ionotropic 5-HT3 receptors (Hurley and Sullivan 2012). Activation of different types of serotonin receptors may decrease or increase excitability in the IC by presynaptic or postsynaptic mechanisms (Hurley 2007;Hurley et al 2008;Wang HT et al 2008). One receptor type that is prominently expressed in the IC is the 5-HT1A receptor (Peruzzi andDut 2004, Smith et al 2014;Thompson et al 1994).…”

Duration Tuning across Vertebrates

“…Serotonin levels in the IC are modulated by behavioral states (Hurley et al, 2002;Peruzzi and Dut, 2004), and activation of serotonin receptors can shift the FSL of IC neurons (Hurley and Pollak, 2005;Hurley, 2007) and modulate GABAergic inhibition (Hurley et al, 2008). This suggests that behavioral state may modulate the responses of DTNs.…”

Acoustic trauma triggers upregulation of serotonin receptor genes

“…For this reason, we compared the relationship of three specific gene pairs between the sham and acoustic trauma groups. The primary comparison of interest was the coexpression of the Gabrg1 and Htr1B genes, since these two receptor types likely function in concert to tune auditory responses (Hurley et al, 2008). Trauma significantly increased the ratios of Htr1B:Gabrg1 from 0.992 to 9.439, (F = 13.510, dF = 1, p = 0.0043, Fig.…”

“…One such neuromodulatory pathway is the serotonergic system. Different serotonergic receptors regulate excitatory inhibitory circuits in specific ways (Hurley, 2007; Hurley et al, 2008; Hurley and Sullivan, 2012), and neuromodulatory plasticity in this system could differentially influence processing pathways following damage. However, there is a relatively poor understanding of how neuromodulatory receptors regulating particular features of excitatory and inhibitory neurotransmission respond to sensory damage, and whether such responses support adaptive models of sensory plasticity.…”

“…For example, the 5-Ht1A receptor decreases excitatory responses and regulates spike timing. The 5-HT1B and the 5-HT2A receptors have both been reported to regulate inhibition; the 1B by disinhibiting neurons (Hurley et al, 2008), the 2A by increasing GABAergic transmission (Wang et al, 2008). Understanding how specific receptors are altered in expression following hearing loss can help develop functional hypotheses on how they contribute to E-I regulation following hearing loss.…”