Biology subjects

Jercog, D.

Publications and source records attributed to Jercog, D..

6 recordsLinked to original sources

bioRxiv2023

The geometry of appetitive-aversive value representations in medial prefrontal networks

The value of rewards and punishments - namely, how good or bad they are perceived - guides approach or avoidance behaviors. Valence refers to the negative or positive "sign" of the state elicited by an event, whereas salience refers to the amount of attention an event attracts, disregarding its valence. While identifying these signals conveys critical information for understanding circuits involved in emotional processing, they are often confounded due to their underlying correlation. Moreover, whereas the study of the neural basis of value coding has been intensively investigated in the appetitive domain, the neural substrates for how aversive values are established for different threat intensities and guide defensive behavior have yet to be discovered. The dorsomedial prefrontal cortex (dmPFC) is a key region in the control of defensive actions, although how different aversive values are encoded at the neuronal level within this region and drive defensive behaviors remains unknown. Here, we developed an instrumental approach/avoidance task in mice that, by matching motivational salience levels elicited by cues predicting rewards or punishments, allows univocally disentangling the presence of either salience, valence, or value coding from brain signals. We performed freely moving large neuronal population calcium imaging in the dmPFC of mice performing our task, conducting appetitive/aversive outcome devaluation/revaluation behavioral tests. We found that, while a similar fraction of single neurons decoded valence and value information, and only a minor fraction decoded salience, value coding was observed at the neuronal population level. Moreover, different value representations of the same valence lay within similar subspaces of the neural state space while values of opposed valence were encoded in orthogonal subspaces, unveiling how the brain stores associative appetitive and aversive information in medial prefrontal networks.

neuroscience↗

bioRxiv2022

Brainstem somatostatin-expressing cells control the emotional regulation of pain behavior

In threatening situations, animals exhibit a broad range of behavioral and autonomic responses. As such, a crucial adaptive response is the inhibition of pain, which facilitates relevant defensive behaviors that promote survival. Whereas the structures and mechanisms involved in fear and pain behaviors are well documented, little is known about the precise neuronal mechanisms mediating the emotional regulation of endogenous pain-suppression. Here, we used a combination of behavioral, anatomical, optogenetic, and electrophysiological approaches to investigate, in male mice, the role of somatostatin-expressing cells in the ventrolateral periaqueductal gray matter (SST+ vlPAG cells) in the control of analgesia induced during defensive states. Our data indicate that optogenetic inhibition of SST+ vlPAG cells promotes analgesia irrespective of animal defensive state. In contrast, optogenetic activation of long-range SST+ vlPAG cells that project to the rostral ventromedial medulla (RVM) abolishes the analgesia mediated by fear behavior. Together, these results identify a novel circuit mechanism composed of long-range SST+ vlPAG cells projecting to the RVM that regulate analgesia elicited during defensive states.

neuroscience↗

bioRxiv2022

Basal amygdala inputs to the medial prefrontal cortex mediate fear memory strengthening

Survival critically depends on the memorization of stimuli recurrently predicting pleasant or aversive experiences. Memory strengthening by additional learning is a critical process allowing the long-term stabilization of learned aversive experience. However, the underlying neuronal circuits and mechanisms are still largely unknown. Using a combination of single unit recordings and optogenetic manipulations, we observed that strengthened fear responses following successive fear learning episodes led to a remapping in the population of basal amygdala (BA) neurons encoding the conditioned stimulus. Moreover, strengthened fear responses were preferentially carried by BA neurons projecting to the medial prefrontal cortex (mPFC). Selective optogenetic inhibition of BA terminals in the mPFC during a second learning episode prevented fear memory strengthening. Together, our findings suggest that fear memory strengthening with additional training critically depends on the selective remapping of a subpopulation of BA neurons projecting to the mPFC.

neuroscience↗

bioRxiv2021

Selection of active defensive behaviors relies on extended amygdala dopamine D2 receptors

The ability to efficiently switch from one defensive strategy to another maximizes an animals chance of survival. Here, we demonstrate that the selection of active defensive behaviors requires the coordinated activation of dopamine D2 receptor (D2R) signaling within the central extended amygdala (EA) comprising the nucleus accumbens, the oval bed nucleus stria terminals and the central amygdala. We find that discriminative learning between predictive and non-predictive threat auditory stimuli is unaltered in mice carrying a temporally-controlled deletion of D2R within output neurons of the EA. In contrast, intact EA D2R signaling is required for active avoidance learning and innate flight responses triggered by a visual threat stimulus (looming). Consequently, conditional D2R knockout mice biased defensive responses toward passive defensive strategies. Altogether, these findings identify EA D2R signaling as an important mechanism by which DA regulates the switch from passive to active defensive behaviors, regardless whether of learned or innate threat.

neuroscience↗

bioRxiv2019

Modulation of cortical slow oscillatory rhythm by GABAB receptors: an experimental and computational study

Slow wave oscillations (SWO) dominate cortical activity during deep sleep, anesthesia and in some brain lesions. SWO consist of Up states or periods of activity interspersed with Down states or periods of silence. The rhythmicity expressed during SWO integrates neuronal and connectivity properties of the network and it is often altered in neurological pathological conditions. Different mechanisms have been proposed to drive the transitions between Up and Down states, in particular, adaptation mechanisms have been proposed to contribute to the Up-to-Down transition. Synaptic inhibition, and specially GABAB receptors, have also been proposed to have a role in the termination of Up states. The interplay between these two potential mechanisms, adaptation and inhibition, is not well understood and the role of slow inhibition is not yet clear regarding the full cycle of the slow oscillatory rhythm. Here we contribute to its understanding by combining experimental and computational techniques. GABAB receptors-blockade not only elongated Up states, but also affected the subsequent Down states, and thus the whole cycle of the oscillations. Furthermore, while adaptation tends to yield a rather regular behavior, GABAB receptors-blockade decreased the variability of the sequence of Up and Down states. Interestingly, variability changes could be accomplished in two different ways: either accompanied by a shortening or by a lengthening of the duration of the Down state. Even when the most common observation is the lengthening of the Down states, both changes are expressed experimentally and also in numerical simulations. Our simulations suggest that the sluggishness of GABAB receptors to follow the excitatory fluctuations of the cortical network can explain these different network dynamics modulated by GABAB receptors.

neuroscience↗

bioRxiv2016

UP-DOWN cortical dynamics reflect state transitions in a bistable balanced network

In the idling brain, neuronal circuits often exhibit transitions between periods of sustained firing (UP state) and quiescence (DOWN state). Although these dynamics occur across multiple areas and behavioral conditions, the underlying mechanisms remain unclear. Here we analyze spontaneous population activity from the somatosensory cortex of urethane-anesthetized rats. We find that UP and DOWN periods are variable (i.e. non-rhythmic) and that the population rate shows no significant decay during UP periods. We build a network model of excitatory (E) and inhibitory (I) neurons that exhibits a new bistability between a quiescent state and a balanced state of arbitrarily low rate. Fluctuating inputs trigger state transitions. Adaptation in E cells paradoxically causes a marginal decay of E-rate but a marked decay of I-rate, a signature of balanced bistability that we validate experimentally. Our findings provide evidence of a bistable balanced network that exhibits non-rhythmic state transitions when the brain rests.

neuroscience↗