Input of sensory, limbic, basal ganglia and pallial/cortical information into the ventral/lateral habenula: Functional principles in anuran amphibians

Abstract

The habenula – a phylogenetically old brain structure present in all vertebrates – is involved in pain processing, reproductive behaviors, sleep-wake cycles, stress responses, reward, and learning. We performed intra- and extracellular recordings of ventral habenula (VHb) neurons in the isolated brain of anurans and revealed similar cell and response properties to those reported for the lateral habenula of mammals. We identified tonic regular, tonic irregular, rhythmic firing, and silent VHb neurons. Transitions between these firing patterns were observed during spontaneous activity. Electrical stimulation of various brain areas demonstrated VHb input of auditory, optic, limbic, basal ganglia, and pallial information. This resulted in three different response behaviors in VHb neurons: excitation, inhibition, or alternating facilitation and suppression of neuronal activity. Spontaneously changing activity patterns were observed to modulate, reset, or suppress the response behavior of VHb neurons, indicating a gating mechanism. This could be a network status or context dependent selection mechanism for which information are transmitted to task relevant brain areas (i.e., sensory system, limbic system, basal ganglia). Furthermore, alternating facilitation and suppression sequences upon auditory nerve stimulation correlated positively fictive motor activities recorded via the compound potential of the vagal nerve. Stimulation of the auditory nerve or the habenula led to facilitation, suppression, or alternating facilitation and suppression of neuronal activity in putative dopaminergic neurons. Due to complex habenula feedback loops with basal ganglia, limbic, and sensory systems, the habenula involvement in a variety of functions might therefore be explained by a modulatory effect on a task-relevant input stream.