Novel neurobiological circuit architecture uncovered for flight response

When facing life-threatening stimuli, animals show various types of fear behaviors, ranging from risk assessment and freezing to flight. Freezing, a passive coping strategy, is elicited when the danger stimulus is inescapable, whereas flight, an active defense response, is evoked when the stimulus is controllable or escapable. 

The thalamic reticular nucleus (TRN), a shell-shaped nucleus located between the cortex and the thalamus, is composed of GABAergic neurons, among which parvalbumin-expressing (PV+) neurons predominate. This nucleus functions as the ‘gateway guardian’ in filtering information between the cortex and the thalamus and has been implicated in selective attention, sensorimotor processing, and consciousness. However, whether it participates in the regulation of flight behavior remains largely elusive.

The research team led by Prof. LI Xiaoming from the School of Medicine engaged in research into whether the TRN may be involved in attentional regulation for the selection of relevant sensory information during the fear process. Their findings are published in an article entitled “A novel cortico-intrathalamic circuit for flight behavior” in the journal of Nature Neuroscience.

LI Xiaoming et al. discover that it is activation of parvalbumin-expressing neurons in the limbic TRN rather than those in the sensory TRN that mediates flight. Glutamatergic inputs from the cingulate cortex (Cg) selectively activate the limbic TRN, which in turn inhibits the intermediodorsal thalamic nucleus (IMD). Activation of this Cg→limbic TRN→IMD circuit results in inhibition of the IMD and produces flight behavior. Conversely, removal of inhibition onto the IMD results in more freezing and less flight, suggesting that the IMD may function as a pro-freeze center. Overall, these findings reveal a novel corticothalamic circuit through the TRN that controls the flight response.

These findings are highly applauded by experts both at home and abroad. Comments include “This is a superb research with salient originality and unexpected findings,” “Not only is this research ground-breaking, but it also makes a breakthrough in conceptualization, thus making considerable contributions to the understanding of defensive flight behavior,” and “This research opens the door to research into fear behavior and offers novel approaches to studying how animals make a decision when confronted with a fearful environment.”