Neuronal circuits underlying novelty and familiarity signaling
Susanna Molas Casacuberta
Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School (USA)
Novel stimuli induce an increase in exploratory response that rapidly decreases as the stimulus becomes familiar upon repeated exposures. Novelty exploration and habituation with familiarity are fundamental for the adaptation to changes in the environment and prime goal-directed behaviors. Numerous neurodevelopmental, neuropsychiatric and neurodegenerative disorders exhibit altered response to novelty and disrupted familiarization, including schizophrenia, autism spectrum disorders or Parkinson's disease, among others. However, the brain circuits that control behavioral responses to novelty and familiarity and how these are disrupted in a disease brain remain poorly understood. My work has shown that the interpeduncular nucleus (IPN) of the midbrain represents a neuroanatomical substrate for familiarity signaling. The IPN receives mainly, but not exclusively, afferent projections from the medial habenula (mHb) and together represent a significant pathway that conveys information from the limbic forebrain to midbrain and hindbrain areas involved in affective behaviors, motivation and reward. My research reveals a new role for the IPN and demonstrates that IPN γ-amminobutyric acid (GABA)ergic neurons are activated by repeated exposures to the same stimulus, as it becomes familiar. Using optogenetic tools to specifically manipulate IPN GABAergic neurons, I found that activity of these neurons is both sufficient and necessary for the expression of familiar responses and therefore a critical component of novelty preference. Moreover, familiarity and novelty signaling in the IPN depend on inputs arising from the mHb and the ventral tegmental area, respectively. These results may provide significant insights into the basis of novelty and familiarity responses, which are disrupted in numerous neurological disorders, and set foundations for improved therapeutic interventions.
Host: Jan Tønnesen