Zoe has developed an open-source tool PhaSER, which allows her to perform real-time oscillatory phase estimation and apply optogenetic manipulations at precise phases of hippocampal theta during high-density electrophysiological recordings in head-fixed mice while they navigate a virtual environment. The precise timing of single-unit spiking relative to network-wide oscillations (i.e., phase locking) has long been thought to maintain excitatory-inhibitory homeostasis and coordinate cognitive processes, but due to intense experimental demands, the causal influence of this phenomenon has never been determined. Thus, we developed PhaSER (Phase-locked Stimulation to Endogenous Rhythms), a tool which allows the user to explore the temporal relationship between single-unit spiking and ongoing oscillatory activity.

Coping with threatening situations requires both identifying stimuli predicting danger and selecting adaptive behavioral responses in order to survive. The dorso medial prefrontal cortex (dmPFC) is a critical structure involved in the regulation of threat-related behaviour, yet it is still largely unclear how threat-predicting stimuli and defensive behaviours are associated within prefrontal networks in order to successfully drive adaptive responses. Over the past years, we used a combination we used a combination of extracellular recordings, neuronal decoding approaches, and state of the art optogenetic manipulations to identify key neuronal elements and mechanisms controlling defensive fear responses. I will present an overview of our recent work ranging from analyses of dedicated neuronal types and oscillatory and synchronization mechanisms to artificial intelligence approaches used to decode the activity or large population of neurons. Ultimately these analyses allowed the identification of high dimensional representations of defensive behavior unfolding within prefrontal networks.

Coping with threatening situations requires both identifying stimuli predicting danger and selecting adaptive behavioral responses in order to survive. The dorso medial prefrontal cortex (dmPFC) is a critical structure involved in the regulation of threat-related behaviour, yet it is still largely unclear how threat-predicting stimuli and defensive behaviours are associated within prefrontal networks in order to successfully drive adaptive responses. To address these questions, we used a combination of extracellular recordings, neuronal decoding approaches, and optogenetic manipulations to show that threat representations and the initiation of avoidance behaviour are dynamically encoded in the overall population activity of dmPFC neurons. These data indicate that although dmPFC population activity at stimulus onset encodes sustained threat representations and discriminates threat- from non-threat cues, it does not predict action outcome. In contrast, transient dmPFC population activity prior to action initiation reliably predicts avoided from non-avoided trials. Accordingly, optogenetic inhibition of prefrontal activity critically constrained the selection of adaptive defensive responses in a time-dependent manner. These results reveal that the adaptive selection of active fear responses relies on a dynamic process of information linking threats with defensive actions unfolding within prefrontal networks.

Neural codes, such as temporal codes (precisely timed spikes) and rate codes (instantaneous spike firing rates), are believed to be used in encoding sensory information into spike trains of cortical neurons. Temporal and rate codes co-exist in the spike train and such multiplexed neural code-carrying spike trains have been shown to be spatially synchronized in multiple neurons across different cortical layers during sensory information processing. Inhibition is suggested to promote such synchronization, but it is unclear whether distinct subtypes of interneurons make different contributions in the synchronization of multiplexed neural codes. To test this, in vivo single-unit recordings from barrel cortex were combined with optogenetic manipulations to determine the contributions of parvalbumin (PV)- and somatostatin (SST)-positive interneurons to synchronization of precisely timed spike sequences. We found that PV interneurons preferentially promote the synchronization of spike times when instantaneous firing rates are low (<12 Hz), whereas SST interneurons preferentially promote the synchronization of spike times when instantaneous firing rates are high (>12 Hz). Furthermore, using a computational model, we demonstrate that these effects can be explained by PV and SST interneurons having preferential contribution to feedforward and feedback inhibition, respectively. Overall, these results show that PV and SST interneurons have distinct frequency (rate code)-selective roles in dynamically gating the synchronization of spike times (temporal code) through preferentially recruiting feedforward and feedback inhibitory circuit motifs. The inhibitory neural circuit mechanisms we uncovered here his may have critical roles in regulating neural code-based somatosensory information processing in the neocortex.

Coping with threatening situations requires both identifying stimuli predicting danger and selecting adaptive behavioral responses in order to survive. The dorso medial prefrontal cortex (dmPFC) is a critical structure involved in the regulation of threat-related behaviour, yet it is still largely unclear how threat-predicting stimuli and defensive behaviours are associated within prefrontal networks in order to successfully drive adaptive responses. To address these questions, we used a combination of extracellular recordings, neuronal decoding approaches, and optogenetic manipulations to show that threat representations and the initiation of avoidance behaviour are dynamically encoded in the overall population activity of dmPFC neurons. These data indicate that although dmPFC population activity at stimulus onset encodes sustained threat representations and discriminates threat- from non-threat cues, it does not predict action outcome. In contrast, transient dmPFC population activity prior to action initiation reliably predicts avoided from non-avoided trials. Accordingly, optogenetic inhibition of prefrontal activity critically constrained the selection of adaptive defensive responses in a time-dependent manner. These results reveal that the adaptive selection of active fear responses relies on a dynamic process of information linking threats with defensive actions unfolding within prefrontal networks.