Anatomically heterogeneous populations of CB₁ cannabinoid receptor‐expressing interneurons in the CA3 region of the hippocampus show homogeneous input–output characteristics

Abstract

A subpopulation of GABAergic cells in cortical structures expresses CB 1 cannabinoid receptors (CB 1 ) on their axon terminals. In order to understand the function of these interneurons in information processing, it is necessary to uncover how they are embedded into neuronal circuits. Therefore, the proportion of GABAergic terminals expressing CB 1 and the morphological and electrophysiological properties of CB 1 -immunoreactive interneurons should be revealed. We investigated the ratio and the origin of CB 1 -expressing inhibitory boutons in the CA3 region of the hippocampus. Using immunocytochemical techniques, we estimated that approximately 40 % of GABAergic axon terminals in different layers of CA3 also expressed CB 1 . To identify the inhibitory cell types expressing CB 1 in this region, we recorded and intracellularly-labeled interneurons in hippocampal slices. CB 1 -expressing interneurons showed distinct axonal arborization, and were classified as basket cells, mossyfiber-associated cells, dendritic-layer-innervating cells or perforant-path-associated cells. In each morphological category, a substantial variability in axonal projection was observed. In contrast to the diverse morphology, the active and passive membrane properties were found to be rather similar. Using paired recordings, we found that pyramidal cells displayed large and fast unitary postsynaptic currents in response to activating basket and mossy-fiber-associated cells, while they showed slower and smaller synaptic events in pairs originating from interneurons that innervate the dendritic layer, which may be due to dendritic filtering. In addition, CB 1 activation significantly reduced the amplitude of the postsynaptic currents in each cell pair tested. Our data suggest that CB 1 -expressing interneurons with different axonal projections have comparable physiological characteristics, contributing to a similar proportion of GABAergic inputs along the somato-dendritic axis of CA3 pyramidal cells.3

Extended Interneuronal Network of the Dentate Gyrus

“…These data provide a conceptual framework for the previous anecdotal observations (Hájos and Mody, 1997; Katona et al, 2016; Lasztóczi et al, 2011; Sik et al, 1994; Szabadics and Soltesz, 2009; Szabó et al, 2014; Ceranik et al, 1997; Armstrong et al, 2011) of individual interneurons that possessed axon branches that extended out into neighboring regions from the anatomically defined area where the parent cell bodies were located. Remarkably, the extended interneuronal network as a whole seems to be able to provide both spatially (perisomatic and dendritic) and temporally (Fig 4D) distributed inhibition, likely contributing to the characteristically sparse firing of GCs.…”

“…Within the hippocampal formation, each of the anatomically defined regions such as the dentate gyrus (DG), CA3 and CA1 area has a certain number of “classical” interneurons (e.g., 27,240 in the rat CA1 (Bezaire and Soltesz, 2013)) that regulate local principal cell excitability, whereas long-distance projecting GABA cells from the medial septum and entorhinal cortices exert powerful behavioral state-dependent control over local hippocampal circuits through various disinhibitory gating mechanisms (Basu et al, 2016; Melzer et al, 2012). Interestingly, several studies contain anecdotal observations indicating that axons of hippocampal interneurons sometimes cross the classical anatomically defined areal boundaries (Hájos and Mody, 1997; Katona et al, 2016; Lasztóczi et al, 2011; Sik et al, 1994; Szabadics and Soltesz, 2009; Szabó et al, 2014; Ceranik et al, 1997; Armstrong et al, 2011), indicating the possible existence of a third major GABAergic cell class that extends its influence from the local networks to the immediately adjacent circuits. However, the existence, abundance, cellular composition and functional properties of such an extended, meso-scale (i.e., between local circuit and long-distance) interneuronal system are not well understood.…”

Perisomatic GABAergic synapses of basket cells effectively control principal neuron activity in amygdala networks

“…there were cells, which avoided the perisomatic region and formed synapses only on more distal sites, whereas others innervated exclusively the perisomatic membrane surface. Between these two extremes, the innervation patterns of BCs formed a continuum, therefore categorization of these interneurons into perisomatic and dendrite-targeting cells expressing PV and CCK like in the hippocampus (Cope et al, 2002; Buhl et al, 1994; Szabó et al, 2014) is not possible in the BA. When we analyzed the target distribution of single BCs on multiple postsynaptic cells (Figure 8), we found the same continuous innervation pattern, i.e.…”

“…In the hippocampus, both PVBCs and CCKBCs preferentially innervate the soma and proximal dendrites of pyramidal cells (Halasy et al, 1996; Gulyás et al, 1993; Földy et al, 2010; Szabó et al, 2014). Their dendritic shafts, however, are targeted by different interneurons expressing PV or CCK, whose axonal arbor largely avoids the pyramidal cell layer (Buhl et al, 1994; Halasy et al, 1996; Cope et al, 2002; Szabó et al, 2014).…”

“…Their dendritic shafts, however, are targeted by different interneurons expressing PV or CCK, whose axonal arbor largely avoids the pyramidal cell layer (Buhl et al, 1994; Halasy et al, 1996; Cope et al, 2002; Szabó et al, 2014). The structural segregation of axon clouds of PV- and CCK-expressing GABAergic cells targeting distinct functional (perisomatic vs. dendritic) domains of pyramidal cells secures the division of labor between perisomatic and dendrite-targeting interneurons in the hippocampus.…”