Complementary Roles of Cholecystokinin- and Parvalbumin-Expressing GABAergic Neurons in Hippocampal Network Oscillations

Abstract

In the hippocampal CA1 area, a relatively homogenous population of pyramidal cells is accompanied by a diversity of GABAergic interneurons. Previously, we found that parvalbumin-expressing basket, axo-axonic, bistratified, and oriens-lacunosum moleculare cells, innervating different domains of pyramidal cells, have distinct firing patterns during network oscillations in vivo. A second family of interneurons, expressing cholecystokinin but not parvalbumin, is known to target the same domains of pyramidal cells as do the parvalbumin cells. To test the temporal activity of these independent and parallel GABAergic inputs, we recorded the precise spike timing of identified cholecystokinin interneurons during hippocampal network oscillations in anesthetized rats and determined their molecular expression profiles and synaptic targets. The cells were cannabinoid receptor type 1 immunopositive. Contrary to the stereotyped firing of parvalbumin interneurons, cholecystokinin-expressing basket and dendrite-innervating cells discharge, on average, with 1.7 Ϯ 2.0 Hz during high-frequency ripple oscillations in an episode-dependent manner. During theta oscillations, cholecystokinin-expressing interneurons fire with 8.8 Ϯ 3.3 Hz at a characteristic time on the ascending phase of theta waves (155 Ϯ 81°), when place cells start firing in freely moving animals. The firing patterns of some interneurons recorded in drug-free behaving rats were similar to cholecystokinin cells in anesthetized animals. Our results demonstrate that cholecystokinin-and parvalbumin-expressing interneurons make different contributions to network oscillations and play distinct roles in different brain states. We suggest that the specific spike timing of cholecystokinin interneurons and their sensitivity to endocannabinoids might contribute to differentiate subgroups of pyramidal cells forming neuronal assemblies, whereas parvalbumin interneurons contribute to synchronizing the entire network.

Functional Specificity of Mossy Fiber Innervation of GABAergic Cells in the Hippocampus

“…3) are thought to play complementary roles to FSBCs, because of their different input and output properties (Hefft and Jonas, 2005;Földy et al, 2006;Glickfeld and Scanziani, 2006), regulation by modulatory systems Freund and Katona, 2007;Neu et al, 2007) and in vivo firing properties (Klausberger et al, 2005). In our sample, all RSBCs had the majority of their axons arborizing in the pyramidal cell layer of CA3 (24 of 24; all cells), forming large, closely placed boutons.…”

Serotonergic neuron diversity: Identification of raphe neurons with discharges time-locked to the hippocampal theta rhythm

“…These receptors are expressed by several classes of GABAergic interneurons (23)(24)(25), which have specific functions. Thus, cholecystokinin-containing basket cells, which are also endowed by nicotinic and cannabinoid receptors, are credited for conveying emotional-, mood-, and motivational-related inputs to the network of pyramidal cells (26,27). Serotonin 3 receptors are also expressed on calbindin-and calretinin-containing GABAergic cells (28), which control not only pyramidal cells but other hippocampal inhibitory cells as well (29,30).…”

Behavior-dependent specialization of identified hippocampal interneurons

“…Analysis of network oscillations were performed as described previously 15,47,48 with adjustments for different oscillatory frequencies in drug-free rats. Data processing was done with Spike2 or MATLAB (including the Wavelet Toolbox, version 7.9-R2009b; MathWorks).…”