Early, sustained and broadly-tuned discharge of fast-spiking interneurons in the premotor cortex during action planning

Preparatory neural activity in premotor areas is critical for planning and execution of voluntary movements. Previous studies in monkeys and mice have revealed how the discharges of pyramidal, excitatory neurons (PNs) encode a motor plan for an upcoming movement (Afshar et al., 2011; Chen et al., 2017; Li et al., 2015). However, the contribution of GABAergic interneurons, specifically fast-spiking interneurons (FSNs), to voluntary movements remains poorly understood. Putative premotor areas involved in action planning have been demonstrated in rodents. In particular, in mice, a premotor area controlling voluntary licking has been identified in the anterior-lateral motor cortex (ALM) (Komiyama et al., 2010). Also, ALM partially overlaps with the rostral forelimb area (RFA), the previously defined premotor region involved in the control of paw movement in rats and mice (Rouiller et al., 1993; Tennant et al., 2011). To understand the excitatory-inhibitory microcircuit involved in action planning, here I compare directly the response properties of PNs and FSNs during licking behaviour and forelimb retraction in the mouse. Recordings are carried out with both acute electrodes and chronic microelectrode arrays from both the two premotor areas, i.e. the ALM \u2013 responsible for licking \u2013, and RFA \u2013 involved in paw movement. Specifically, in a first set of experiments, I used head-restrained mice that spontaneously lick a reward delivered at random intervals from a drinking spout. Mice voluntary performed either single isolated or a burst of consecutive licks, which I categorized, a posteriori, in single (= 1 lick) and multiple licks ( 65 3 licks). During the task, I extracellularly recorded single units\u2019 activity from ALM, using acute in vivo electrophysiology. I identified putative PNs and FSNs, based on well-established features of their waveforms, and investigated their functional properties during the movement. Unexpectedly, I report that optogenetically-verified FSNs showed an earlier and more sustained activation than PNs. In particular, most of the neurons\u2019 activity anticipated the licking onset, consistently with an involvement of the ALM in movement planning. The majority of the neurons (~90%) increased their firing frequency in correspondence with the movement, but suppressive modulations were also observed in a subset of units. For both PNs and FSNs, I found significantly greater discharge during multiple than single licks and the peak discharge was significantly delayed for both subclasses during multiple licking events. However, FSNs modulated their activity about 100ms earlier than PNs. Furthermore, almost all FSNs showed a peak in their response before the beginning of the sequence of licks. Analysis of mean information content confirms that FSNs predict licking onset not only significantly better, but even earlier, than PNs. Chronic electrode arrays covering both the ALM and RFA were next used to simultaneously probe neural responses during (i) licking and (ii) forelimb pulling in a robotic device (Spalletti et al., 2017). I report that most of the FSNs respond with a stereotyped increase in their firing rates during both licking and pulling. In stark contrast, PNs show a variety of behaviours, dependent on movement type. At least for a minority of them, licking behaviour and forelimb retraction are represented as two different motor acts, reaching significant levels in the PNs. Accordingly, computational analysis shows that PNs carry more independent information than FSNs. Altogether, these data indicate that a global rise of GABAergic inhibition mediated by FSNs firing contributes to early action planning. Next, encouraged by the deeper understanding of the cortical microcircuits underlying movement planning in mice, I exploited this knowledge to explore more complex mechanisms, as action understanding. The neural circuits that integrate performed and observed actions have been found in the premotor cortex of monkeys and named as \u2018mirror neurons system\u2019 (di Pellegrino et al., 1992). Recently, the presence of mirror neurons have been demonstrated in rodents in the anterior cingulate cortex (Carrillo et al., 2019), but whether they could contribute to action understanding in the premotor cortex is still unclear. At behavioural level, the observation of actions can actually lead, in some cases, to the repetition of those same actions. This phenomenon has been named social facilitation, and the underlying motor program has been attributed to the mirror system (Ferrari et al., 2005). Here, I set up a behavioural task similar to the one exploited in monkeys to explore social facilitation in mice. I took advantage of licking behaviour to set up the social facilitation experiment. Therefore, head-restrained mice were allowed to lick water from a feeding needle. I found that mice can actually facilitated to lick more when another individual was engaged in the same action, supporting the hypothesis of a social facilitation in mouse. Altogether these results indicate that the observers\u2019 behaviour was actually influenced by the demonstrators\u2019 one, laying the groundwork for the study of mirror neurons in mice at cellular level

Sodium hydroxide pretreatment as an effective approach to reduce the dye/holes recombination reaction in P-Type DSCs

We report the synthesis of a novel squaraine dye (VG21-C12) and investigate its behavior as p-type sensitizer for p-type Dye-Sensitized Solar Cells. The results are compared with O4-C12, a well-known sensitizer for p-DSC, and sodium hydroxide pretreatment is described as an effective approach to reduce the dye/holes recombination. Various variable investigation such as dipping time, dye loading, photocurrent, and resulting cell efficiency are also reported. Electrochemical impedance spectroscopy (EIS) was utilized for investigating charge transport properties of the different photoelectrodes and the recombination phenomena that occur at the (un)modified electrode/electrolyte interface

Echocardiographic Screening of Anomalous Origin of Coronary Arteries in Athletes with a Focus on High Take-Off

Anomalous aortic origin of coronary arteries (AAOCA) represents a rare congenital heart disease. However, this disease is the second most common cause of sudden cardiac death in apparently healthy athletes. The aim of this systematic review is to analyze the feasibility and the detection rate of AAOCA by echocardiography in children and adults. A literature search was performed within the National Library of Medicine using the following keywords: coronary artery origin anomalies and echocardiography; then, the search was redefined by adding the keywords: athletes, children, and high take-off. Nine echocardiographic studies investigating AAOCA and a total of 33,592 children and adults (age range: 12-49 years) were included in this review. Of these, 6599 were athletes (12-49 years). All studies demonstrated a high feasibility and accuracy of echocardiography for the evaluation of coronary arteries origin as well as their proximal tracts. However, some limitations exist: the incidence of AAOCA varied from 0.09% to 0.39% (up to 0.76%) and was lower than described in computed tomography series (0.3-1.8%). Furthermore, echocardiographic views for the evaluation of AAOCA and the definition of minor defects (e.g., high take-off coronary arteries) have not been standardized. An echocardiographic protocol to diagnose the high take-off of coronary arteries is proposed in this article. In conclusion, the screening of AAOCA by echocardiography is feasible and accurate when appropriate examinations are performed; however, specific acoustic windows and definitions of defects other than AAOCA need to be standardized to improve sensitivity and specificity

Combining robotics with enhanced serotonin-driven cortical plasticity improves post-stroke motor recovery.

Despite recent progresses in robotic rehabilitation technologies, their efficacy for post-stroke motor recovery is still limited. Such limitations might stem from the insufficient enhancement of plasticity mechanisms, crucial for functional recovery. Here, we designed a clinically relevant strategy that combines robotic rehabilitation with chemogenetic stimulation of serotonin release to boost plasticity. These two approaches acted synergistically to enhance post-stroke motor performance. Indeed, mice treated with our combined therapy showed substantial functional gains that persisted beyond the treatment period and generalized to non-trained tasks. Motor recovery was associated with a reduction in electrophysiological and neuroanatomical markers of GABAergic neurotransmission, suggesting disinhibition in perilesional areas. To unveil the translational potentialities of our approach, we specifically targeted the serotonin 1A receptor by delivering Buspirone, a clinically approved drug, in stroke mice undergoing robotic rehabilitation. Administration of Buspirone restored motor impairments similarly to what observed with chemogenetic stimulation, showing the immediate translational potential of this combined approach to significantly improve motor recovery after stroke

Baseline haematological and biochemical reference values for healthy male adults from Mali

Introduction: Haematological reference values are very important for diagnostic orientation and treatment decision. The aim of this study was to establish haematological reference values for Malian healthy adults. Methods: A cross-sectional study including 161 male Malians aged between 19 and 54 years old was performed. Median and reference ranges were calculated for haematological and biochemical parameters. Parametric student's t-test was used to determine any statistically significant differences by age, smoker status, body mass index (BMI) and occupation. Ranges were further compared with those reported for other African, Afro-American and Caucasian populations. Results: Increased levels of MCV, MCH, PLT and EOS were found in younger Malians who had abnormal BMI and altered platelets parameters. Notably, significantly lower eosinophil and monocyte counts were observed in Malians compared to Europeans The smoking status did not seem to directly affect RIs. Conclusion: This is the first study to determine normal laboratory parameters in Malian adult males. Our results underscore the necessity of establishing region-specific clinical reference ranges that would allow clinicians and practitioners to manage laboratory tests, diagnosis and therapies. These data are useful not only for the management of patients in Mali, but also to support European and American clinicians in the health management of asylum seekers and migrants from Mali