Temporal organization of neuronal activity in the prefrontal – hypothalamic – midbrain circuit and its role in the regulation of innate behaviors

• Applicant: Professor Dr. Alexey Ponomarenko, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Experimental and Theoretical Network Neuroscience
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 517326017

Innate behaviours, including feeding, interactions with conspecifics, and exploratory behaviours, involve integration of signals about bodily state and environmental cues in the lateral hypothalamus (LH). Prominent descending inputs to LH arise from the medial prefrontal cortex (mPFC), a region essential for biasing behavioural choices in an adaptively relevant way. Earlier work by others and our group in mPFC and our recent studies in LH showed that neuronal activity in these regions is temporally organized by network oscillations. Depending on their coherence, oscillations can facilitate or diminish neuronal signaling between brain regions. Yet hypothalamic neuronal dynamics regulating diverse innate behaviours and the read-out of prefrontal signals in the hypothalamus are elusive. Moreover, during spontaneous behaviour, the interactions between neurons in the lateral hypothalamus (LH) and the ventral tegmental area (VTA), two crucial components of the reward circuitry, are unknown. Using a combination of high-density dual-site neuronal recordings in behaving mice, machine learning analysis of behaviour and neural decoding as well as optogenetics, we aim at investigating the functional role of the neuronal synchronisation between the mPFC, lateral aspects of the hypothalamus and the VTA. We will focus on beta oscillations (15–30 Hz) that we recently observed across this circuit. A traditional approach of measuring firing of hypothalamic neurons across behaviors will be combined with studies of spike timing according to phases of network oscillations. The neural decoding of various aspects of innate behavior will be used to unravel firing rate and temporal codes in the mPFC-LH-VTA circuit. The role of these neuronal interactions in the engagement in innate behaviors according to the current behavioral alternatives, i.e., social interaction vs. food intake or novel object exploration, will be studied using optogenetic manipulations of mPFC projections in the LH in a behavior-contingent closed-loop fashion. Our work will reveal the temporal organization and the behavioural role of descending signalling by excitatory cortical afferents and their read-out by vital subcortical circuits governing innate behaviours.

• DFG Programme: Research Grants