Involvement of the gabargic septo-hippocampal pathway in brain stimulation reward

Resumen

The hippocampus is a structure mostly related to novelty detection, associative and spatial learning, and memory processes, but not very much is known about hippocampal mechanisms underlying positive reinforcement during brain stimulation reward. Although the anatomical relationships between the septum and the hippocampus through the septo-hippocampal pathway are well established, the functional relationship with behavior remains poorly understood. In turn, the septum is classically related to its capability to generating and maintaining brain stimulation reward by electrical stimulation. To explore the contribution of the hippocampus to brain stimulation reward, transgenic J20 (this model have a deficit of GABAergic septo-hippocampal projections) and wild-type C57 mice were stimulated through electrodes implanted in Schaffer collaterals, and field postsynaptic potentials (fPSPs) were recorded from electrodes implanted in the hippocampal CA1 area before, during, and after a brain stimulation reward task. Brain stimulation reward consisted of an operant conditioning paradigm using as reinforcement trains at 100 Hz applied to the medial septum through the stimulating electrode. The hippocampal synaptic efficiency was determined from changes in the field excitatory and inhibitory postsynaptic potential (fEPSP and fIPSP) components of the fPSPs evoked at the CA3-CA1 along the acquisition of the brain stimulation reward protocol. Successive rewarding sessions evoked a progressive decrease in the amplitude of fEPSPs in an inverse relationship with the increase in brain stimulation reward performance. Additionally, we evaluated the rhythmic activity of the hippocampus in a preference task, comparing the rewarding effects of 8 Hz, 20 Hz, and 100 Hz trains of electrical stimulation. The evaluation of hippocampal electroencephalographic recordings (EEGs) associated with brain stimulation reward performance demonstrates the clear preference for 100 Hz, as seen from the increase of the low theta and the decrease of low gamma bands. These results were supported by the transgenic J20 model and replicated by intra-hippocampal injections of a GABAB antagonist in C57 mice, supporting the notion of a significant involvement of GABAB receptors in brain stimulation reward. As a whole, it has been shown here that i) the GABAergic septo-hippocampal pathway participates in the transmission of information necessary for septal brain stimulation reward, as well as for preference processing between different reinforcements, by its effect through hippocampal GABAB receptors; ii) the hippocampus is actively involved not only in the learning of brain stimulation reward, but also in the evaluation of its reinforcement value.