The Role of the Central Histaminergic System in Behavioral State Control

Arrigoni, Elda; Fuller, Patrick M.

doi:10.1007/7854_2021_263

Cited by 5 publications

(5 citation statements)

References 135 publications

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“…We have previously explored how levels of arousal are altered following chemogenetic manipulation of this TMN HDC projection (Yu et al, 2015), and found that activation of the TMN HDC projection increased motor activity, and that genetic knockdown of vgat from this pathway sustains wakefulness. We do not know why our work differs from the findings of Venner et al 2019, who found, that chemogenetic manipulation of hdc cells did not affect sleep-wake behaviour and found no role for GABA in wakefulness, since after knockout of gad and vgat genes from hdc cells there was no behavioural phenotype (Venner et al, 2019; Arrigoni and Fuller, 2021).…”

Section: Discussioncontrasting

confidence: 95%

“…Histamine, a wake-specific neuromodulator, is produced in tuberomammillary nucleus (TMN) neurons of the posterior hypothalamus (Watanabe et al, 1983; Panula et al, 1984; Haas and Panula, 2003; Scammell et al, 2019; Yoshikawa et al, 2021). These neurons send axons throughout the brain (Takagi et al, 1986; Airaksinen and Panula, 1988; Haas and Panula, 2003; Arrigoni and Fuller, 2021; Yoshikawa et al, 2021), and are defined by expression of the histidine decarboxylase ( hdc ) gene, which encodes the enzyme that synthesizes histamine (Joseph et al, 1990). Histamine is released from axonal varicosities (Takagi et al, 1986), and activates excitatory H1, H2 and inhibitory H3 metabotropic receptors (Haas and Panula, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Co-release of histamine and GABA in prefrontal cortex excites fast-spiking interneurons and causes divisive gain change in pyramidal cells; an effect that is enhanced in older mice

Lucaci

Chadderton

Wisden

et al. 2022

Preprint

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We studied how co-release of histamine/GABA from axons originating from the hypothalamic tuberomammillary nucleus (TMN) and projecting to the prefrontal cortex (PFC) influences circuit processing. We opto-stimulated histamine/GABA co-release from genetically defined TMN axons that express the histidine decarboxylase gene (TMNHDC axons). Whole-cell recordings were used to monitor excitability of visually identified PFC neurons in layer 2/3 of prelimbic (PL), anterior cingulate (AC) and infralimbic (IL) regions before and after opto-stimulated histamine/GABA release. We found that histamine-GABA co-release influences the PFC through actions on distinct neuronal types: histamine stimulates fast-spiking interneurons; and co-released GABA enhances tonic (extrasynaptic) inhibition on pyramidal cells (PyrNs). For fast spiking non-accommodating interneurons, opto-stimulation increased excitability, an effect blocked by histamine H1 and H2 receptor antagonists. The excitability of other interneuron types in the PFC was not altered. In contrast, the combined action of histamine and GABA co-release from TMNHDC axons produced predominantly divisive gain changes in PyrNs, increasing their resting input conductance, and decreasing the slope of the input-output relationship. The direct inhibitory effect of TMNHDC axon activation on PyrNs was not blocked by histamine receptor antagonists but was blocked by GABAA receptor antagonists. Across the adult lifespan (from 3 months to over 2 years of age), stimulation of TMNHDCaxons in the PFC inhibited PyrN excitability significantly more in older mice. For individuals that maintain cognitive performance into later life, increases in TMNHDC modulation of PyrNs could enhance information processing and be an adaptive mechanism to buttress cognition.

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Section: Discussioncontrasting

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Co-release of histamine and GABA in prefrontal cortex excites fast-spiking interneurons and causes divisive gain change in pyramidal cells; an effect that is enhanced in older mice

Lucaci

Chadderton

Wisden

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…We have previously explored how levels of arousal are altered following chemogenetic manipulation of this TMN HDC projection (Yu et al, 2015), and found that activation of the TMN HDC projection increased motor activity, and that genetic knockdown of vgat from this pathway sustains wakefulness. In contrast, Venner et al 2019 reported that chemogenetic manipulation of hdc cells did not affect sleep-wake behaviour and found no role for GABA in wakefulness (Venner et al, 2019;Arrigoni and Fuller, 2021).…”

Section: Discussionmentioning

confidence: 97%

“…Histamine, a wake-specific neuromodulator, is produced by tuberomammillary nucleus (TMN) neurons of the posterior hypothalamus (Watanabe et al, 1983;Panula et al, 1984;Haas and Panula, 2003;Scammell et al, 2019;Yoshikawa et al, 2021) that send axons throughout the brain (Takagi et al, 1986;Airaksinen and Panula, 1988;Haas and Panula, 2003;Arrigoni and Fuller, 2021;Yoshikawa et al, 2021), and are defined by expression of the histidine decarboxylase (hdc) gene, which encodes the enzyme that synthesizes histamine (Joseph et al, 1990). Histamine is released from axonal varicosities (Takagi et al, 1986), and activates excitatory H1, H2 and inhibitory H3 metabotropic receptors (Haas and Panula, 2016).…”

Section: Introductionmentioning

confidence: 99%

Histamine Release in the Prefrontal Cortex Excites Fast-Spiking Interneurons while GABA Released from the Same Axons Inhibits Pyramidal Cells

Lucaci

Chadderton

et al. 2022

J. Neurosci.

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We studied how histamine and GABA release from axons originating from the hypothalamic tuberomammillary nucleus (TMN) and projecting to the prefrontal cortex (PFC) influence circuit processing. We optostimulated histamine/GABA from genetically defined TMN axons that express the histidine decarboxylase gene (TMNHDCaxons). Whole-cell recordings from PFC neurons in layer 2/3 of prelimbic, anterior cingulate, and infralimbic regions were used to monitor excitability before and after optostimulated histamine/GABA release in male and female mice. We found that histamine-GABA release influences the PFC through actions on distinct neuronal types: the histamine stimulates fast-spiking interneurons; and the released GABA enhances tonic (extrasynaptic) inhibition on pyramidal cells (PyrNs). For fast-spiking nonaccommodating interneurons, histamine released from TMNHDCaxons induced additive gain changes, which were blocked by histamine H1 and H2 receptor antagonists. The excitability of other fast-spiking interneurons in the PFC was not altered. In contrast, the GABA released from TMNHDCaxons predominantly produced divisive gain changes in PyrNs, increasing their resting input conductance, and decreasing the slope of the input–output relationship. This inhibitory effect on PyrNs was not blocked by histamine receptor antagonists but was blocked by GABAAreceptor antagonists. Across the adult life span (from 3 to 18 months of age), the GABA released from TMNHDCaxons in the PFC inhibited PyrN excitability significantly more in older mice. For individuals who maintain cognitive performance into later life, the increases in TMNHDCGABA modulation of PyrNs during aging could enhance information processing and be an adaptive mechanism to buttress cognition.SIGNIFICANCE STATEMENTThe hypothalamus controls arousal state by releasing chemical neurotransmitters throughout the brain to modulate neuronal excitability. Evidence is emerging that the release of multiple types of neurotransmitters may have opposing actions on neuronal populations in key cortical regions. This study demonstrates for the first time that the neurotransmitters histamine and GABA are released in the prefrontal cortex from axons originating from the tuberomammillary nucleus of the hypothalamus. This work demonstrates how hypothalamic modulation of neuronal excitability is maintained throughout adult life, highlighting an unexpected aspect of the aging process that may help maintain cognitive abilities.

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“…One of the neurotransmitters that is profoundly affected by stress is histamine which is classically associated to different physiological functions, such as the sleep-wake cycle, sensory and motor functions, energy and endocrine homeostasis, cognition and attention (Arrigoni and Fuller, 2021;Nomura et al, 2019;Panula and Nuutinen, 2013;Provensi et al, 2020;Venner et al, 2019;Yoshikawa et al, 2021). Early experimental evidence has shown that histaminergic neurons, exclusively located in the hypothalamic tuberomammillary nucleus (TMN), significantly increase their activity in rats exposed to acute stress (Mazurkiewicz-Kwilecki and Prell, 1986).…”

Section: Introductionmentioning

confidence: 99%

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

Aceto

Nardella

Lazzarino

et al. 2022

Neurobiology of Disease

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The Role of the Central Histaminergic System in Behavioral State Control

Cited by 5 publications

References 135 publications

Co-release of histamine and GABA in prefrontal cortex excites fast-spiking interneurons and causes divisive gain change in pyramidal cells; an effect that is enhanced in older mice

Co-release of histamine and GABA in prefrontal cortex excites fast-spiking interneurons and causes divisive gain change in pyramidal cells; an effect that is enhanced in older mice

Histamine Release in the Prefrontal Cortex Excites Fast-Spiking Interneurons while GABA Released from the Same Axons Inhibits Pyramidal Cells

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

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