Serotonin is implicated in mood and affective disorders. However, growing evidence suggests that a core endogenous role is to promote flexible adaptation to changes in the causal structure of the environment, through behavioral inhibition and enhanced plasticity. We used long-term photometric recordings in mice to study a population of dorsal raphe serotonin neurons, whose activity we could link to normal reversal learning using pharmacogenetics. We found that these neurons are activated by both positive and negative prediction errors, and thus report signals similar to those proposed to promote learning in conditions of uncertainty. Furthermore, by comparing the cue responses of serotonin and dopamine neurons, we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Our findings show how the activity patterns of serotonin neurons support a role in cognitive flexibility, and suggest a revised model of dopamine–serotonin opponency with potential clinical implications.

While miniature inertial sensors offer a promising means for precisely detecting, quantifying and classifying animal behaviors, versatile inertial sensing devices adapted for small, freely-moving laboratory animals are still lacking. We developed a standalone and cost-effective platform for performing high-rate wireless inertial measurements of head movements in rats. Our system is designed to enable real-time bidirectional communication between the headborne inertial sensing device and third party systems, which can be used for precise data timestamping and low-latency motion-triggered applications. We illustrate the usefulness of our system in diverse experimental situations. We show that our system can be used for precisely quantifying motor responses evoked by external stimuli, for characterizing head kinematics during normal behavior and for monitoring head posture under normal and pathological conditions obtained using unilateral vestibular lesions. We also introduce and validate a novel method for automatically quantifying behavioral freezing during Pavlovian fear conditioning experiments, which offers superior performance in terms of precision, temporal resolution and efficiency. Thus, this system precisely acquires movement information in freely-moving animals, and can enable objective and quantitative behavioral scoring methods in a wide variety of experimental situations.

Head movements are primarily sensed in a reference frame tied to the head, yet they are used to calculate self-orientation relative to the world. This requires to re-encode head kinematic signals into a reference frame anchored to earth-centered landmarks such as gravity, through computations whose neuronal substrate remains to be determined. Here, we studied the encoding of self-generated head movements in the rat caudal cerebellar vermis, an area essential for graviceptive functions. We found that, contrarily to peripheral vestibular inputs, most Purkinje cells exhibited a mixed sensitivity to head rotational and gravitational information and were differentially modulated by active and passive movements. In a subpopulation of cells, this mixed sensitivity underlay a tuning to rotations about an axis defined relative to gravity. Therefore, we show that the caudal vermis hosts a re-encoded, gravitationally polarized representation of self-generated head kinematics in freely moving rats.

Numerous achievements in biology have resulted from the evolution of biophotonics, a general term describing the use of light in the study of living systems. Over the last fifteen years, biophotonics has progressively blended with molecular genetics to give rise to optogenetics, a set of techniques enabling the functional study of genetically-defined cellular populations, compartments or processes with optical methods. In neuroscience, optogenetics allows real-time monitoring and control of the activity of specific neuronal populations in a wide range of animal models. This technical breakthrough provides a new level of sophistication in experimental approaches in the field of fundamental neuroscience, significantly enhancing our ability to understand the complexity of neuronal circuits.

Inertial sensors are increasingly used in rodent research, in particular for estimating head orientation relative to gravity, or head tilt. Despite this growing interest, the accuracy of tilt estimates computed from rodent head inertial data has never been assessed. Using readily available inertial measurement units mounted onto the head of freely moving rats, we benchmarked a set of tilt estimation methods against concurrent 3D optical motion capture. We show that, while low-pass filtered head acceleration signals only provided reliable tilt estimates in static conditions, sensor calibration combined with an appropriate choice of orientation filter and parameters could yield average tilt estimation errors below $1.5$${}^{\circ }$ during movement. We then illustrate an application of inertial head tilt measurements in a preclinical rat model of unilateral vestibular lesion and propose a set of metrics describing the severity of associated postural and motor symptoms and the time course of recovery. We conclude that headborne inertial sensors are an attractive tool for quantitative rodent behavioral analysis in general and for the study of vestibulo-postural functions in particular.

Optogenetic neuromodulation techniques, which have emerged during the last 15 years, have considerably enhanced our ability to probe the functioning of neural circuits by allowing the excitation and inhibition of genetically-defined neuronal populations using light. Having gained tremendous popularity in the field of fundamental neuroscience, these techniques are now opening new therapeutic avenues. Optogenetic neuromodulation is a method of choice for studying the physiopathology of neurological and neuropsychiatric disorders in a range of animal models, and could accelerate the discovery of new therapeutic strategies. New therapeutic protocols employing optogenetic neuromodulation may also emerge in the near future, offering promising alternative approaches for disorders which lack appropriate treatments, such as pharmacoresistant epilepsy and inherited retinal degeneration.