Cellular resilience: 5-HT neurons in Tph2^−/− mice retain normal firing behavior despite the lack of brain 5-HT

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• 作者：Alberto Montalbano^a ; Jonas Waider^b ; Mario Barbieri^c ; Ozan Baytas^b ; Klaus-Peter Lesch^b ; Renato Corradetti^a ; Boris Mlinar^a ; ^{bmlinar@unifi.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tph2 null mice ; Neuron firing ; Dorsal raphe ; Membrane channels ; Ih ; Electrophysiology
• 刊名：European Neuropsychopharmacology
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：25
• 期：11
• 页码：2022-2035
• 全文大小：2084 K

文摘

Considerable evidence links dysfunction of serotonin (5-hydroxytryptamine, 5-HT) transmission to neurodevelopmental and psychiatric disorders characterized by compromised "social" cognition and emotion regulation. It is well established that the brain 5-HT system is under autoregulatory control by its principal transmitter 5-HT via its effects on activity and expression of 5-HT system-related proteins. To examine whether 5-HT itself also has a crucial role in the acquisition and maintenance of characteristic rhythmic firing of 5-HT neurons, we compared their intrinsic electrophysiological properties in mice lacking brain 5-HT, i.e. tryptophan hydroxylase-2 null mice (Tph2^−/−) and their littermates, Tph2^+/− and Tph2^+/+, by using whole-cell patch-clamp recordings in a brainstem slice preparation and single unit recording in anesthetized animals. We report that the active properties of dorsal raphe nucleus (DRN) 5-HT neurons in vivo (firing rate magnitude and variability; the presence of spike doublets) and in vitro (firing in response to depolarizing current pulses; action potential shape) as well as the resting membrane potential remained essentially unchanged across Tph2 genotypes. However, there were subtle differences in subthreshold properties, most notably, an approximately 25% higher input conductance in Tph2^−/− mice compared with Tph2^+/− and Tph2^+/+ littermates (p<0.0001). This difference may at least in part be a consequence of slightly bigger size of the DRN 5-HT neurons in Tph2^−/− mice (approximately 10%, p<0.0001). Taken together, these findings show that 5-HT neurons acquire and maintain their signature firing properties independently of the presence of their principal neurotransmitter 5-HT, displaying an unexpected functional resilience to complete brain 5-HT deficiency.