class="head no_bottom_margin" id="sec1title">IntroductionThe cornu ammonis 2 (CA2) hippocampal region has distinctive molecular, physiological, and connectivity properties (). CA2 pyramidal cells respond vigorously to direct entorhinal inputs from layer II stellate cells (, ). In addition, they receive a direct mossy fiber connection from granule cells and contribute to a parallel trisynaptic circuit to deep CA1 sublayers (, ). Recurrently associated with CA3, CA2 pyramidal cells project to superficial layers of the medial entorhinal cortex (). γ-Aminobutyric acid-ergic (GABAergic) innervation by local parvalbumin-expressing cells and specific classes of dendritic-targeting interneurons is particularly prominent in this region (, , ), supporting strong inhibitory control (, ). CA2 is specifically targeted by hypothalamic fibers releasing vasopressin and oxytocin during social interaction (, , ) and by supramammillary glutamatergic cells with a major role in wake-sleep regulation (, href="#bib49" rid="bib49" class=" bibr popnode">Soussi et al., 2010).Given recurrent connections with these brain systems, CA2 can be considered a network hub. Not surprisingly, it is involved in a diversity of functions, including spatial and social memory. Place fields are more abundant but less precise in CA2 than in CA3 and CA1 (href="#bib38" rid="bib38" class=" bibr popnode">Oliva et al., 2016a). Some studies have revealed that CA2 ensemble firing changes prominently over time (href="#bib1" rid="bib1" class=" bibr popnode">Alexander et al., 2016, href="#bib26" rid="bib26" class=" bibr popnode">Lee et al., 2015, href="#bib29" rid="bib29" class=" bibr popnode">Lu et al., 2015, href="#bib30" rid="bib30" class=" bibr popnode">Mankin et al., 2015). In contrast, others have reported some cells firing in place during brief exploratory pauses and over sleep (href="#bib24" rid="bib24" class=" bibr popnode">Kay et al., 2016). This leads to the idea that CA2 is specialized in bridging contextual representations, supporting their contribution to episodic memory function (href="#bib30" rid="bib30" class=" bibr popnode">Mankin et al., 2015, href="#bib56" rid="bib56" class=" bibr popnode">Wintzer et al., 2014). When CA2 cells are specifically manipulated, defects emerge in contextual habituation to a neutral environment (href="#bib3" rid="bib3" class=" bibr popnode">Boehringer et al., 2017), but not for contextual fear memory or spatial learning (href="#bib18" rid="bib18" class=" bibr popnode">Hitti and Siegelbaum, 2014). Instead, memory for a familiar conspecific is affected. Such a social memory role may reflect not only specific features of CA2 (href="#bib27" rid="bib27" class=" bibr popnode">Leroy et al., 2017) but also downstream effects (href="#bib37" rid="bib37" class=" bibr popnode">Okuyama et al., 2016, href="#bib44" rid="bib44" class=" bibr popnode">Raam et al., 2017). Possibly, CA2 is instrumental in interfacing among brain systems, but the mechanisms are not known.The heterogeneous oscillatory behavior of putative CA2 cells was reported using extracellular recordings (href="#bib24" rid="bib24" class=" bibr popnode">Kay et al., 2016, href="#bib39" rid="bib39" class=" bibr popnode">Oliva et al., 2016b, href="#bib38" rid="bib38" class=" bibr popnode">Oliva et al., 2016a). Moreover, in evaluating proximodistal changes of firing similarity between contexts, a significant spatial in-homogeneity was found at the CA3a-CA2 border (href="#bib29" rid="bib29" class=" bibr popnode">Lu et al., 2015). Unfortunately, without morphological confirmation, it is difficult to interpret these results given the miscellaneous composition of this transitional area (href="#bib54" rid="bib54" class=" bibr popnode">Valero et al., 2015). Here, we reveal striking heterogeneity of cell-type-specific molecular markers around dorsal CA2 in rats and use intracellular and extracellular in vivo recordings followed by neurochemical identification to target this region. We found marked proximodistal trends of synaptic activity and theta/gamma oscillations in both subthreshold membrane potentials and phase-locked firing. Our data disclose opposing entrainment by different current generators and GABAergic microcircuits across the proximal and distal sectors. Moreover, we found that these trends shape CA2 pyramidal cell state-dependent oscillatory activity and place coding.
展开▼
