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

Alberto Montalbano; Jonas Waider; Mario Barbieri; Ozan Baytas; Klaus-Peter Lesch; Renato Corradetti; Boris Mlinar

doi:10.1016/j.euroneuro.2015.08.021

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

Alberto Montalbano, Jonas Waider, Mario Barbieri, Ozan Baytas, Klaus-Peter Lesch, Renato Corradetti, Boris Mlinar^*

^*Corresponding author for this work

MHeNs - Neuroscience

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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

Original language	English
Pages (from-to)	2022-2035
Journal	European Neuropsychopharmacology
Volume	25
Issue number	11
DOIs	https://doi.org/10.1016/j.euroneuro.2015.08.021
Publication status	Published - Nov 2015

Keywords

Tph2 null mice
Neuron firing
Dorsal raphe
Membrane channel
I-h
Electrophysiology

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10.1016/j.euroneuro.2015.08.021

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title = "Cellular resilience: 5-HT neurons in Tph2(-/-) mice retain normal firing behavior despite the lack of brain 5-HT",

abstract = "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",

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author = "Alberto Montalbano and Jonas Waider and Mario Barbieri and Ozan Baytas and Klaus-Peter Lesch and Renato Corradetti and Boris Mlinar",

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AU - Montalbano, Alberto

AU - Waider, Jonas

AU - Barbieri, Mario

AU - Baytas, Ozan

AU - Lesch, Klaus-Peter

AU - Corradetti, Renato

AU - Mlinar, Boris

PY - 2015/11

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KW - Tph2 null mice

KW - Neuron firing

KW - Dorsal raphe

KW - Membrane channel

KW - I-h

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JF - European Neuropsychopharmacology

IS - 11

ER -

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

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Keywords

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