Oral Presentation The International Congress of Neuroendocrinology 2014

Nucleus incertus and relaxin-3 - an emerging modulatory role in arousal , stress and memory (#13)

Sherie Ma 1
  1. Florey Neuroscience Institutes, University Of Melbourne, VIC, Australia

The nucleus incertus (NI) of the pontine periventricular grey consists of GABAergic neurons with long-range ascending projections to forebrain. Efferent and afferent connections implicate the NI in processes of ‘behavioural planning, habenular function, hippocampal/cortical activity in attention/memory, and in oculomotor control’. The NI is a site of corticotropin releasing-factor (CRF) action, and forms a neural circuit positioned to modulate arousal/stress responses and the de/synchronization of hippocampal theta rhythm, an oscillatory activity (4-12 Hz) prominent in the electroencephalograph (EEG) during exploration and memory processes. Theta rhythm underlies goal-oriented behaviour and cognition, and is a neurophysiological signature of REM sleep. The NI is also a primary site for neurons expressing the neuropeptide, relaxin-3, which can modulate septohippocampal activity and theta rhythm and are associated with spatial working memory in the rat. However, NI function in awake, behaving animals remains unclear.

Therefore, we used a pharmacogenetic approach (i.e. designer receptors exclusively activated by designer drugs, DREADDs) to modulate NI activity in freely-moving rats and assessed the behavioural and physiological consequences. An adeno-associated viral vector was used to transduce a modified human muscarinic receptor, hM3Dq, into NI neurons of adult male rats. For behavioural and EEG recordings, hM3Dq was activated by the specific DREADD ligand, clozapine-N-oxide (CNO).

In hM3Dq-expressing rats, NI activation with CNO produced long-lasting theta activity, associated with increased locomotor activity, with significantly greater and persistent horizontal and vertical plane activity, but not increased movement velocity, suggesting effects related to increased arousal and impairment of habituation and rest. Current studies are examining effects of NI activation on tests of spatial and emotional memory, anxiety/aversive behaviour, and associated neural activity, along with comparative studies of NI inactivation with hM4Di.

Current data suggest NI activity regulates behavioural state and I will review our findings on this emerging integrative neural network and its therapeutic potential.