Hippocampal interneurons co-express transcripts encoding the α7 nicotinic receptor subunit and the cannabinoid receptor 1

Abstract

The notion of functional interactions between the α7 nicotinic acetylcholine (α7 nACh) and the cannabinoid systems is emerging from recent in vitro and in vivo studies. Both the α7 nACh receptor and the cannabinoid receptor 1 (CB1) are highly expressed in the hippocampus. To begin addressing possible anatomical interactions between the α7 nACh and the cannabinoid systems in the rat hippocampus, we investigated the distribution of neurons expressing α7 nACh mRNA in relation to those containing CB1 mRNA. By in situ hybridization we found that the α7 nACh mRNA is diffusely expressed in principal neurons and is highly expressed in a subset of interneurons. We observed that the pattern of distribution of hippocampal interneurons co-expressing transcripts encoding α7 nACh and glutamate decarboxylase (GAD; synthesizing enzyme of GABA) closely resembles the one displayed by interneurons expressing CB1 mRNA. By double in situ hybridization we established that the majority of hippocampal interneurons expressing α7 nACh mRNA have high levels of CB1 mRNA. As CB1 interneurons contain cholecystokinin (CCK), we investigated the degree of cellular co-expression of α7 nACh mRNA and CCK, and found that the cellular co-existence of α7 nACh and CCK varies within the different layers of the hippocampus.In summary, we established that most of the hippocampal α7 nACh expressing interneurons are endowed with CB1 mRNA. We found that these α7 nACh/CB1 interneurons are the major subpopulation of hippocampal interneurons expressing CB1 mRNA. The α7 nACh expressing interneurons represent half of the detected population of CCK containing neurons in the hippocampus. Since it is well established that the vast majority of hippocampal interneurons expressing CB1 mRNA have 5-HT type 3 (5-HT 3 ) receptors, we conclude that these hippocampal α7 nACh/5HT 3 /CB1/CCK interneurons correspond to those previously postulated to relay inputs from diverse cortical and subcortical regions about emotional, motivational, and physiological states. KeywordsCB1; 5-HT3 receptors; 5-HT; CCK; Alzheimer's disease; schizophrenia Nicotinic acetylcholine (nACh) receptors are members of the superfamily of ligand-gated ion channels that the includes the GABA receptors (GABA A and GABA C ), the glycine receptor and the 5-HT type 3 receptor (5-HT 3 R). In the nervous system, several subunits of the nACh receptor have been identified, including nine α subunits (α2-α10) and three β subunits (β2-β4) (Sargent, 1993;McGehee and Role, 1995 (Sargent, 1993;McGehee and Role, 1995). Electrophysiological, pharmacological and genetic approaches demonstrated that the homomeric α7-nACh receptor has a high affinity for α-bungarotoxin (Couturier et al., 1990;Séguéla et al., 1993;Chen and Patrick, 1997;Orr-Urtreger et al., 1997). The high affinity of the α7-nACh receptor for α-bungarotoxin has been used to map the distribution of this receptor in several brain areas, including the hippocampus (Hunt and Schmidt, 1978;Freedman et al., 1993;Fabian-Fine et al., 2001). Although mRNA enco...

Serotonin dependent masking of hippocampal sharp wave ripples

“…The delayed SPW-R appearance is due to their masking by serotonin in a dose dependent manner, which compares well to effects on sharp waves in in vivo hippocampal EEG recordings (Richter-Levin and Segal, 1990). The effect was dependent on 5-HT 1A or 5-HT 2A/C receptor activation but insensitive to activation of excitatory 5-HT 3 receptors, which are expressed on subtypes of interneurons (Turner et al, 2004;Morales et al, 1996Morales et al, , 2007Chittajallu et al, 2013).…”

An acetylcholine alpha7 positive allosteric modulator rescues a schizophrenia-associated brain endophenotype in the 15q13.3 microdeletion, encompassing CHRNA7

“…dopamine and norepinephrine (Hajos and Rogers, 2010). Post-synaptic nAChA7Rs have been found on inhibitory GABAergic interneurons where they facilitate neuronal functioning (Morales et al, 2008). A reduced number of nAChA7Rs might result in reduction of inhibition and a consequent increase in excitability could lead to the deficient sensory and overall inhibition and epilepsy (Stevens et al, 2015) and to cognitive and learning disturbances observed in schizophrenia (Feuerbach et al, 2009).…”

Cannabinoids Reveal Separate Controls for Whisking Amplitude and Timing in Rats

“…CB1R is not expressed in layer 5b of S1. The basal ganglia contain high levels of CB1R (Egertova and Elphick 2000;Herkenham et al 1990;Marsicano and Lutz 1999;Morales et al 2007;Tsou et al 1998) and receive inputs both from somatosensory (S1) and motor (M1) cortices (Alloway et al 2006). The pontine nuclei (Pn), which contain CB1R expressing neurons (Cristino et al 2006), receive inputs from CB1R regions of S1 (layer 5b; Mercier et al 1990) and M1 (layer 5; Legg et al 1989).…”

“…Whereas the basal ganglia, cerebellum, neocortex, and hippocampus contain high levels of CB1R (Egertova and Elphick 2000;Herkenham et al 1990; Marsicano and Lutz 1999;Morales et al 2007;Tsou et al 1998), CB1R expression in the thalamus and brain stem is relatively sparse . Furthermore, CB1R expression varies along the cortical surface and between cortical layers (Bodor et al 2005;Lafourcade et al 2007).…”