<p>Persistent and maladaptive fear in the absence of a threat can be disruptive because it decreases an organism’s opportunity to seek life-sustaining substances. Learned safety signaling can suppress fear and encourage reward-seeking behavior, thus freeing the organism from fear induced immobilization. The infralimbic (IL) region of the prefrontal cortex is important for recalling fear extinction memories and for suppressing fear via learned safety signals. Neurons in the IL show an excitatory response to an extinguished fear cue. We thus hypothesized that neurons in the IL would encode safety by showing an excitatory response during active fear suppression to a learned safety signal. </p> <p>To assess global changes in IL activity, we monitored IL multi-unit activity to different cues while training animals in a fear-reward-safety discrimination task (Sangha, Chadick, & Janak, 2013). During the discrimination task, male rats learned that the reward cue predicted liquid sucrose, the fear cue predicted footshock and the joint presentation of both the fear and safety cues resulted in no footshock. We also counterbalanced the modality of fear and safety cues (auditory vs visual) with two separate groups of animals to control for potential sensory modality effects. Male rats showed high levels of freezing to the fear cue, and significantly reduced levels of freezing to the combined fear+safety cue. Male rats also showed high levels of port activity to the reward cue. There was no significant difference in the learning rate between the two counterbalanced conditions. </p> <p>Our multi-unit-data showed an increase in IL neuronal firing to the fear+safety cue across training sessions. This effect was consistent between the two counterbalanced conditions. We also examined single-unit activity from all animals that received light as the safety cue (n=8). This allowed us to examine the population response profile with a subset of the total animals. Although not statistically significant, our preliminary single-unit data demonstrated a decrease in the percentage of neurons that showed an inhibitory response to the fear+safety cue, but no change in the percentage of neurons that showed an excitatory response to the fear+safety cue. There was also no change in the magnitude of averaged firing rate in fear+safety excitatory or inhibitory neurons across training. Taken together, the decreased inhibition of single-unit activity in the IL may drive the increased excitation in multi-unit activity in the IL during behavioral fear suppression to a safety signal. </p>

Tous les réseaux de neurones immatures génèrent une activité dite « spontanée »qui persiste même en l’absence de toute afférence et est impliquée dans de nombreux processus développementaux. Cette activité apparaît in vitro sous formes de vagues calciques ou électriques pouvant se propager sur de grandes distances et embraser toute la préparation. Toutefois, sa dynamique a été assez peu étudiée jusqu’à présent. En vue de combler quelque peu cette lacune, nous avons utilisé des matrices de microélectrodes (MEA) pour caractériser l’activité rythmique spontanée dans la moelle épinière embryonnaire de souris, sur des préparations aigues et en culture incluant également le tronc cérébral.Les enregistrements MEA produisent des volumes de données très importants qui nécessitent des outils d’analyse performants et adaptés à l’information que l’on souhaite extraire. Nous avons donc développé des méthodes pour la détection, la classification et la cartographie des patrons spatiotemporels d’activité dans les données multicanaux. Notre approche cartographique utilise l’interpolation par splines et est orientée vers la production de cartes multimodales combinant l’activité électrique et des données anatomiques ou biochimiques (marquages). Ces méthodes d’analyse nous ont permis de décrire très précisément l’évolution de l’activité spontanée aux stades précoces (E12.5–E15.5). Nous avons également montré que, à E14.5, l’activité est initiée dans le bulbe, plus précisément dans une région riche en neurones 5-HT, suggérant un nouveau rôle des voies sérotoninergiques descendantes dans la maturation des réseaux spinaux.Enfin, nous avons analysé les mouvements embryonnaires à E14.5 et avons découvert des caractéristiques analogues à la dynamiques spatiotemporelle des activités intraspinales. / Immature neural networks generate a peculiar type of activity that persists even in the absence of electrical inputs and was termed for this reason “endogenous”or “spontaneous”. This activity is ubiquitous and was found involved in a wide range of developmental events. In vitro, it can be observed as calcium or electrical waves propagating over great distances, often invading the whole preparation,but its dynamics remain poorly described. In order to somewhat fill this gap,we used multielectrode arrays (MEAs) to characterise the spontaneous rhythmic activity in the mouse developing spinal cord, in both acute and cultured isolated hindbrain-spinal cord preparations.To extract relevant information from the massive amounts of data yielded by MEA recordings, adapted analysis tools are needed. Thus, we have developedmethods for the detection, classification and mapping of spatiotemporal patternsof activity in multichannel data. Our mapping approach is based on the thin plates pline interpolation and includes the possibility to combine maps of activity with anatomical or stained data for multimodal imaging.These methods allowed us to analyse in great detail the evolution of spontaneousactivity at early stages (E12.5–E15.5). In addition, we have localised theinitiation site of E14.5 activity in the medulla and shown that it matches a densemidline population of serotoninergic neurons, suggesting a new role for 5-HTpathways in the maturation of spinal networks. Finally, we have recorded andtracked spontaneous limb movements of E14.5 embryos and found that features of motility were consistent with patterns of spinal activity.