Acute restraint stress impairs histamine type 2 receptor ability to increase the excitability of medium spiny neurons in the nucleus accumbens

Aceto, Giuseppe; Nardella, Luca; Lazzarino, Giacomo; Tavazzi, Barbara; Bertozzi, Alessia; Nanni, Simona; Colussi, Claudia; D’Ascenzo, Marcello; Grassi, Claudio

doi:10.1016/j.nbd.2022.105932

Cited by 3 publications

(1 citation statement)

References 74 publications

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“…Western blot experiments were performed as previously described [37]. Briefly, tissues were lysed in ice-cold lysis buffer (NaCl 150 mM, Tris-HCl 50 mM pH 7.4, EDTA 2 mM) containing 1% Triton X-100, 0.1% SDS, 1 × protease inhibitor cocktail (Sigma-Aldrich, St Louis, MO, USA), 1 mM sodiumorthovanadate (Sigma-Aldrich) and 1 mM sodium fluoride (Sigma-Aldrich).…”

Section: Western-blot Assaymentioning

confidence: 99%

Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens

Aceto,

Nardella,

Nanni

et al. 2024

Cell. Mol. Life Sci.

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It has been recently established that GPR158, a class C orphan G protein-coupled receptor, serves as a metabotropic glycine receptor. GPR158 is highly expressed in the nucleus accumbens (NAc), a major input structure of the basal ganglia that integrates information from cortical and subcortical structures to mediate goal-directed behaviors. However, whether glycine modulates neuronal activity in the NAc through GPR158 activation has not been investigated yet. Using whole-cell patch-clamp recordings, we found that glycine-dependent activation of GPR158 increased the firing rate of NAc medium spiny neurons (MSNs) while it failed to significantly affect the excitability of cholinergic interneurons (CIN). In MSNs GPR158 activation reduced the latency to fire, increased the action potential half-width, and reduced action potential afterhyperpolarization, effects that are all consistent with negative modulation of potassium M-currents, that in the central nervous system are mainly carried out by Kv7/KCNQ-channels. Indeed, we found that the GPR158-induced increase in MSN excitability was associated with decreased M-current amplitude, and selective pharmacological inhibition of the M-current mimicked and occluded the effects of GPR158 activation. In addition, when the protein kinase A (PKA) or extracellular signal-regulated kinase (ERK) signaling was pharmacologically blocked, modulation of MSN excitability by GPR158 activation was suppressed. Moreover, GPR158 activation increased the phosphorylation of ERK and Kv7.2 serine residues. Collectively, our findings suggest that GPR158/PKA/ERK signaling controls MSN excitability via Kv7.2 modulation. Glycine-dependent activation of GPR158 may significantly affect MSN firing in vivo, thus potentially mediating specific aspects of goal-induced behaviors.

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Section: Western-blot Assaymentioning

confidence: 99%

Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens

Aceto,

Nardella,

Nanni

et al. 2024

Cell. Mol. Life Sci.

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Ketamine metabolite alleviates morphine withdrawal-induced anxiety via modulating nucleus accumbens parvalbumin neurons in male mice

Chen,

Yan,

Wei

et al. 2023

Neurobiology of Disease

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Suppression of excitatory synaptic transmission in the centrolateral amygdala via presynaptic histamine H3 heteroreceptors

Zhang,

Ling,

Shen

et al. 2024

The Journal of Physiology

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The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole‐cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)‐Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC‐δ‐ and SOM‐positive CeL neurons. The histamine‐induced effect is mediated by H3 receptors expressed on VGLUT1‐/VGLUT2‐positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. imageKey points Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC‐δ‐ and SOM‐positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1‐ or VGLUT2‐positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)–CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.

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Acute restraint stress impairs histamine type 2 receptor ability to increase the excitability of medium spiny neurons in the nucleus accumbens

Cited by 3 publications

References 74 publications

Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens

Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens

Ketamine metabolite alleviates morphine withdrawal-induced anxiety via modulating nucleus accumbens parvalbumin neurons in male mice

Suppression of excitatory synaptic transmission in the centrolateral amygdala via presynaptic histamine H3 heteroreceptors

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