The GABAergic Septohippocampal Pathway Is Directly Involved in Internal Processes Related to Operant Reward Learning

Abstract

We studied the role of γ-aminobutyric acid (GABA)ergic septohippocampal projections in medial septum (MS) self-stimulation of behaving mice. Self-stimulation was evoked in wild-type (WT) mice using instrumental conditioning procedures and in J20 mutant mice, a type of mouse with a significant deficit in GABAergic septohippocampal projections. J20 mice showed a significant modification in hippocampal activities, including a different response for input/output curves and the paired-pulse test, a larger long-term potentiation (LTP), and a delayed acquisition and lower performance in the MS self-stimulation task. LTP evoked at the CA3-CA1 synapse further decreased self-stimulation performance in J20, but not in WT, mice. MS self-stimulation evoked a decrease in the amplitude of field excitatory postsynaptic potentials (fEPSPs) at the CA3-CA1 synapse in WT, but not in J20, mice. This self-stimulation-dependent decrease in the amplitude of fEPSPs was also observed in the presence of another positive reinforcer (food collected during an operant task) and was canceled by the local administration of an antibody-inhibiting glutamate decarboxylase 65 (GAD65). LTP evoked in the GAD65Ab-treated group was also larger than in controls. The hippocampus has a different susceptibility to septal GABAergic inputs depending on ongoing cognitive processes, and the GABAergic septohippocampal pathway is involved in consummatory processes related to operant rewards.

Monoclonal antibodies to 65kDa glutamate decarboxylase induce epitope specific effects on motor and cognitive functions in rats

“…Uptake of antibodies by neurons including Purkinje cells has been recently demonstrated [11] and we confirmed antibody uptake by the AF5 rat mesencephalic cell line. Our recent in vivo studies support the cellular uptake of GAD65Ab as b78 injected in the CA3-CA1 area was detected in hippocampal interneurons [40]. Future studies are planned to investigate the cellular localization of monoclonal GAD65Ab injected in the cerebellar nuclei.…”

Alterations of neurotransmitter norepinephrine and gamma-aminobutyric acid correlate with murine behavioral perturbations related to bisphenol A exposure

“…They demonstrated that context-induced reinstatement of cocaine-seeking was diminished by GABA agonists, either into the dorsal CA3 area or into the LS and VTA areas. Vega-Flores et al reported that the hippocampus has a different susceptibility to septal GABAergic inputs, depending on ongoing cognitive processes, and the GABAergic septohippocampal pathway is involved in consummatory behavior processes related to operant rewards [42]. In the present study, we demonstrated that the "nocturnal corner visit duration without drinking" was correlated with the GABA level in the hippocampus.…”

Pathogenic Roles of Glutamic Acid Decarboxylase 65 Autoantibodies in Cerebellar Ataxias

“…Subsequently, internalization of IgGs has been confirmed in the rat cerebellum [48], in autopsied human cerebellar tissue [49], after interventricular injection of human IgGs in guinea pigs [50], and after peripheral administration of human IgGs in rats [51] (Table 2). We have confirmed the internalization of human monoclonal GAD65Ab b78 by cultured AF5 cells [35]; moreover, b78 has been detected in CA1 interneurons and PCs shortly after its injection in the medial septum/diagonal band and ipsilateral interpositus nucleus, respectively [7, 52]. Differences in neuronal cell types, antibody concentration, and detection methods may account for these contradicting results.…”