Electrical Coupling among Irregular-Spiking GABAergic Interneurons Expressing Cannabinoid Receptors

Cholinergic interneurons (CINs) are essential elements of striatal circuits and behaviors. While acetylcholine signaling via muscarinic receptors (mAChRs) have been well studied, more recent data indicate that postsynaptic nicotinic receptors (nAChRs) located on GABAergic interneurons (GINs) are equally critical. One demonstration is that CINs stimulation induces large disynaptic inhibition of SPNs mediated by nAChR activation of striatal GINs. While these circuits are ideally positioned to modulate striatal output activity, the neurons involved are not definitively identified due largely to an incomplete mapping of CINs-GINs interconnections. Here, we show that CINs optogenetic activation evokes an intricate dual mechanism involving co-activation of pre- and postsynaptic mAChRs and nAChRs on four GINs populations. Using multi-optogenetics, we demonstrate the participation of tyrosine hydroxylase-expressing GINs in the disynaptic inhibition of SPNs likely via heterotypic electrical coupling with neurogliaform interneurons. Altogether, our results highlight the importance of CINs in regulating GINs microcircuits via complex synaptic/heterosynaptic mechanisms.

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Presynaptic Inhibition of GABAA Receptor-Mediated Unitary IPSPs by Cannabinoid Receptors at Synapses Between CCK-Positive Interneurons in Rat Hippocampus

Journal of Neurophysiology ◽

10.1152/jn.00156.2007 ◽

2007 ◽

Vol 98 (2) ◽

pp. 861-869 ◽

Cited By ~ 41

Author(s):

Afia B. Ali

Keyword(s):

Cannabinoid Receptors ◽

Cannabinoid Receptor ◽

Electrical Coupling ◽

Cb1 Receptor ◽

Spike Timing ◽

Rat Hippocampus ◽

Stratum Radiatum ◽

Synaptic Interactions ◽

Immunofluorescence Labeling ◽

Endogenous Cannabinoid

There is growing evidence to link cholecystokinin (CCK)-positive interneurons and anxiety disorders. Despite this, little is known about the physiology and pharmacology of synaptic interactions between CCK-positive interneurons. This study aims to investigate the local circuit connections among CCK-positive Schaffer collateral associated (SCA) interneurons in stratum radiatum (SR) and their modulatory interactions using paired whole cell recordings combined with biocytin and double immunofluorescence labeling in slices of rat hippocampus. The cell bodies of SCA interneurons were located in SR, and their sparsely spiny dendrites projected toward s. pyramidale (SP) and along SR. Their axons innervated SR, SP, and s. oriens (SO) with predominant ramification in SR. These cells were immunopositive for CCK and immunonegative for parvalbumin (PV). SCA interneurons often displayed an accommodating firing pattern with or without a “sag” in response to hyperpolarizing current injection. Pairs of these cells exhibited electrical coupling and reciprocal chemical connections in which inhibitory postsynaptic potentials (IPSPs) displayed powerful frequency-dependent facilitation and augmentation. The synaptic connections were modulated by the endogenous cannabinoid receptor (CB) agonist, anandamide and by depolarization-induced suppression of inhibition (DSI), both of which reduced the amplitude of unitary IPSPs to 50% of control and increased the number of apparent failures of transmission. These effects were blocked by the CB1 receptor antagonist, AM-251. I suggest that synaptic facilitation between CCK-positive SCA interneurons may modify the onset of CB1 receptor-mediated regulation of inhibition, thereby affecting spike timing, and that this process could influence the expression of anxiety.

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