Similar to V the temporal neocortex of mammals including

Similar to V1, the temporal neocortex of mammals, including the primary auditory cortex (A1), is densely innervated by 5-HT fibers originating mainly in the dorsal raphe nucleus (Campbell et al., 1987, Harding and Paxinos, 2004, Törk, 1990), and the major bapta am of 5-HTRs are expressed throughout the temporal neocortex/A1 (Barnes and Sharp, 1999, Basura et al., 2008, Clemett et al., 2000, Cornea-Hébert et al., 1999, García-Oscos et al., 2015, Kilpatrick et al., 1987, Leysen et al., 1982, Malgouris et al., 1993). Studies in bats subjected to an auditory fear conditioning paradigm have shown that 5-HT and 5-HTRs exert potent, gating effects on receptive field plasticity in A1 (Ji and Suga, 2007). Further, 5-HT2A receptors facilitate NMDA receptor (NMDAR)-dependent synaptic potentiation at thalamocortical synapses between the mediodorsal thalamus and prefrontal cortex in mice (Barre et al., 2016). The thalamocortical auditory system between the medial geniculate nucleus (MGN) and A1 of rodents readily expresses NMDAR-dependent LTP in both juvenile and adult animals (Hogsden and Dringenberg, 2009a, Hogsden and Dringenberg, 2009b, Soutar et al., 2016, Speechley et al., 2007). LTP in this system has been suggested to mediate receptive field plasticity and other learning-related adjustments in synaptic connectivity following auditory experiences (Tzounopoulos et al., 2012). To the best of our knowledge, the role of different 5-HTRs on LTP in this system has not been addressed. Thus, we examined the effects of blockade of several classes of 5-HTRs (5-HT1ARs, 5-HT2Rs, and 5-HT3Rs) on the induction of LTP at thalamocortical and intracortical synapses in the A1 of adult rats in vivo.
Results
Discussion The present experiments examined the role of several classes of 5-HTRs on plasticity induction in the thalamocortical auditory system of adult, urethane-anesthetized rats. Delivery of TBS to the MGN reliably induced moderate levels of potentiation of fPSPs recorded in A1. Local application of the broad-acting 5-HTR antagonist methiothepin suppressed LTP at both thalamocortical and intracortical synapses in A1. In fact, rather than LTP, TBS elicited LTD during methiothepin application, an effect that was mimicked by the selective 5-HT2R antagonist ketanserin, but not the 5-HT1AR blocker WAY 100635. Interestingly, antagonism of 5-HT3Rs by granisetron inhibited LTP at thalamocortical, but not intracortical A1 synapses. Further, in the absence of TBS, granisetron application resulted in a pronounced increase in the amplitude of both fPSP peaks, suggesting an inhibitory role of 5-HT3Rs in controlling baseline synaptic transmission at thalamocortical and intracortical A1 synapses. Together, these results indicate that 5-HTRs exert important gating functions by influencing the induction and direction of long-term plasticity at synapses of the fully matured A1 of mammalian species. We were surprised that application of WAY 100635, a highly selective antagonist at 5-HT1ARs (Forster et al., 1995), did not affect LTP induction in A1. 5-HT1ARs act as somatodendritic autoreceptors that suppress 5-HT release, but are also present postsynaptically in the forebrain (Barnes and Sharp, 1999, Nichols and Nichols, 2008). Activation of 5-HT1ARs has been implicated in plasticity/LTP modulation in several forebrain areas, including the hippocampus, visual cortex, and prefrontal cortex. For example, in V1, 5-HT1ARs have been shown to inhibit LTP induction in vitro and in vivo (Gagolewicz and Dringenberg, 2016, Edagawa et al., 1998, Kim et al., 2006), suggesting that 5-HT may participate in the stabilization of synaptic connectivity in the mature cortex. Similarly, in the prefrontal cortex, 5-HT1AR activation can inhibit calcium influx though NMDA channels, thereby reducing the probability of LTP induction and favouring LTD (Meunier et al., 2017). Based on the present results, 5-HT1ARs do not perform similar functions at either thalamocortical or intracortical synapses in the mature A1, at least under the present experimental conditions.