Direct excitation of parvalbumin‐positive interneurons by M1 muscarinic acetylcholine receptors: roles in cellular excitability, inhibitory transmission and cognition. (16th July 2014)

• Record Type: Journal Article
• Authors: Yi, Feng; Ball, Jackson; Stoll, Kurt E.; Satpute, Vaishali C.; Mitchell, Samantha M.; Pauli, Jordan L.; Holloway, Benjamin B.; Johnston, April D.; Nathanson, Neil M.; Deisseroth, Karl; Gerber, David J.; Tonegawa, Susumu; Lawrence, J. Josh
• Is Part Of: Journal of physiology. Volume 592:Number 16(2014:Aug.)
• Page Start: 3463
• Page End: 3494
• Publication Date: 2014-07-16
• Subjects: Physiology -- Periodicals; 612.005
• DOI: 10.1113/jphysiol.2014.275453
• Languages: English
• ISSNs: 0022-3751

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="tjp6231-sec-0010" sec-type="section"> <title>Key points</title> <p> <list id="tjp6231-list-0001" list-type="bullet"> <list-item> <p>Parvalbumin‐containing (PV) neurons from mouse CA1 hippocampus (HC) and prefrontal cortex exhibit a fast spiking phenotype <italic>in vitro</italic>. Within CA1, HC PV cells are mainly comprised of basket and bistratified cell types.</p> </list-item> <list-item> <p>Direct activation of muscarinic acetylcholine receptors (mAChRs) enhances excitability more in CA1 HC than in prefrontal cortex PV cells.</p> </list-item> <list-item> <p>mAChR‐induced excitation of CA1 PV cells occurs through direct activation of M<sub>1</sub> mAChRs.</p> </list-item> <list-item> <p>Transgenetic deletion of M<sub>1</sub> mAChRs from PV cells diminishes M<sub>1</sub> mAChR expression and cholinergic excitation of CA1 PV cells.</p> </list-item> <list-item> <p>mAChR‐induced excitation exclusively in PV cells enhances GABAergic transmission in CA1 pyramidal cells.</p> </list-item> <list-item> <p> <italic>In vivo</italic> activation of M<sub>1</sub> mAChRs in PV cells is important in recognition and working memory but not spatial memory.</p> </list-item> </list> </p> </sec> <sec id="tjp6231-sec-0020" sec-type="section"> <title>Abstract</title> <p>Parvalbumin‐containing (PV) neurons, a major class of GABAergic interneurons, are essential circuit elements of learning networks. As levels of acetylcholine rise during active learning tasks, PV neurons become increasingly engaged in network dynamics. Conversely, impairment of either cholinergic or PV interneuron function induces learning deficits. Here, we examined PV interneurons in hippocampus (HC) and prefrontal cortex (PFC) and their modulation by muscarinic acetylcholine receptors (mAChRs). HC PV cells, visualized by crossing PV‐CRE mice with Rosa26YFP mice, were anatomically identified as basket cells and PV bistratified cells in the stratum pyramidale; in stratum oriens, HC PV cells were electrophysiologically distinct from somatostatin‐containing cells. With glutamatergic transmission pharmacologically blocked, mAChR activation enhanced PV cell excitability in both CA1 HC and PFC; however, CA1 HC PV cells exhibited a stronger postsynaptic depolarization than PFC PV cells. To delete M<sub>1</sub> mAChRs genetically from PV interneurons, we created PV‐M<sub>1</sub> knockout mice by crossing PV‐CRE and floxed M<sub>1</sub> mice. The elimination of M<sub>1</sub> mAChRs from PV cells diminished M<sub>1</sub> mAChR immunoreactivity and muscarinic excitation of HC PV cells. Selective cholinergic activation of HC PV interneurons using Designer Receptors Exclusively Activated by Designer Drugs technology enhanced the frequency and amplitude of inhibitory synaptic currents in CA1 pyramidal cells. Finally, relative to wild‐type controls, PV‐M<sub>1</sub> knockout mice exhibited impaired novel object recognition and, to a lesser extent, impaired spatial working memory, but reference memory remained intact. Therefore, the direct activation of M<sub>1</sub> mAChRs on PV cells contributes to some forms of learning and memory.</p> </sec> </abstract>