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Histamine Release in the Prefrontal Cortex Excites Fast-Spiking Interneurons while GABA Released from the Same Axons
Diana Lucaci1, Xiao Yu1, Paul Chadderton2
1Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom.
Summary
Histamine and GABA from the hypothalamus modulate prefrontal cortex circuits. Histamine excites interneurons, while GABA inhibits pyramidal cells, with GABA
Area of Science:
- Neuroscience
- Neurophysiology
- Neurochemistry
Background:
- The hypothalamus regulates arousal via neurotransmitter release.
- Emerging evidence suggests co-released neurotransmitters can have opposing effects.
- The tuberomammillary nucleus (TMN) is a key hypothalamic arousal center.
Purpose of the Study:
- To investigate the influence of histamine and GABA co-release from hypothalamic tuberomammillary nucleus (TMN) axons on prefrontal cortex (PFC) circuit processing.
- To determine the distinct roles of histamine and GABA in modulating neuronal excitability in the PFC.
- To examine how aging affects TMN-PFC circuit modulation.
Main Methods:
- Optogenetic stimulation of genetically defined TMN axons expressing histidine decarboxylase (TMNHDC).
- Whole-cell recordings from PFC neurons (layer 2/3) in male and female mice.
- Pharmacological blockade of histamine and GABA receptors.
Main Results:
- Histamine released from TMNHDC axons stimulates fast-spiking interneurons via H1/H2 receptors.
- GABA released from TMNHDC axons enhances tonic inhibition in pyramidal cells (PyrNs) via GABAA receptors.
- GABAergic inhibition of PyrNs is significantly stronger in older mice (3-18 months).
Conclusions:
- Hypothalamic histamine and GABA differentially modulate PFC neuronal excitability.
- Aging enhances GABAergic inhibition of PyrNs, potentially supporting cognitive function.
- This study reveals a novel mechanism of hypothalamic neuromodulation across the lifespan.
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