Goal-Oriented Behaviour: The Ventral Tegmental Area in Motivated Movements.

The ventral tegmental area is a midbrain region known for the involvement of its dopaminergic neurons in encoding reward-related features, value and motivational states. New research suggests a role for inhibitory neurons of the ventral tegmental area in the orchestration of head movements, which might be instrumental in guiding animals towards spatial targets during motivated behaviour.

Genetically Defined Functional Modules for Spatial Orienting in the Mouse Superior Colliculus.

In order to explore and interact with their surroundings, animals need to orient toward specific positions in space. Throughout the animal kingdom, head movements represent a primary form of orienting behavior. The superior colliculus (SC) is a fundamental structure for the generation of orienting responses, but how genetically distinct groups of collicular neurons contribute to these spatially tuned behaviors remains largely to be defined. Here, through the genetic dissection of the murine SC, we identify a functionally and genetically homogeneous subclass of glutamatergic neurons defined by the expression of the paired-like homeodomain transcription factor Pitx2. We show that the optogenetic stimulation of Pitx2ON neurons drives three-dimensional head displacements characterized by stepwise, saccade-like kinematics. Furthermore, during naturalistic foraging behavior, the activity of Pitx2ON neurons precedes and predicts the onset of spatially tuned head movements. Intriguingly, we reveal that Pitx2ON neurons are clustered in an orderly array of anatomical modules that tile the entire intermediate layer of the SC. Such a modular organization gives origin to a discrete and discontinuous representation of the motor space, with each Pitx2ON module subtending a defined portion of the animal's egocentric space. The modularity of Pitx2ON neurons provides an anatomical substrate for the convergence of spatially coherent sensory and motor signals of cortical and subcortical origins, thereby promoting the recruitment of appropriate movement vectors. Overall, these data support the view of the superior colliculus as a selectively addressable and modularly organized spatial-motor register.

Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output.

Neural organoids have the potential to improve our understanding of human brain development and neurological disorders. However, it remains to be seen whether these tissues can model circuit formation with functional neuronal output. Here we have adapted air-liquid interface culture to cerebral organoids, leading to improved neuronal survival and axon outgrowth. The resulting thick axon tracts display various morphologies, including long-range projection within and away from the organoid, growth-cone turning, and decussation. Single-cell RNA sequencing reveals various cortical neuronal identities, and retrograde tracing demonstrates tract morphologies that match proper molecular identities. These cultures exhibit active neuronal networks, and subcortical projecting tracts can innervate mouse spinal cord explants and evoke contractions of adjacent muscle in a manner dependent on intact organoid-derived innervating tracts. Overall, these results reveal a remarkable self-organization of corticofugal and callosal tracts with a functional output, providing new opportunities to examine relevant aspects of human CNS development and disease.

Crawling towards a map of the brain.

State-of-the-art techniques reveal a simple circuit of neurons controls the muscle contractions that allow fruit fly larvae to crawl.

Calcium Imaging of Neuronal Activity in Drosophila Can Identify Anticonvulsive Compounds.

Although there are now a number of antiepileptic drugs (AEDs) available, approximately one-third of epilepsy patients respond poorly to drug intervention. The reasons for this are complex, but are probably reflective of the increasing number of identified mutations that predispose individuals to this disease. Thus, there is a clear requirement for the development of novel treatments to address this unmet clinical need. The existence of gene mutations that mimic a seizure-like behaviour in the fruit fly, Drosophila melanogaster, offers the possibility to exploit the powerful genetics of this insect to identify novel cellular targets to facilitate design of more effective AEDs. In this study we use neuronal expression of GCaMP, a potent calcium reporter, to image neuronal activity using a non-invasive and rapid method. Expression in motoneurons in the isolated CNS of third instar larvae shows waves of calcium-activity that pass between segments of the ventral nerve cord. Time between calcium peaks, in the same neurons, between adjacent segments usually show a temporal separation of greater than 200 ms. Exposure to proconvulsants (picrotoxin or 4-aminopyridine) reduces separation to below 200 ms showing increased synchrony of activity across adjacent segments. Increased synchrony, characteristic of epilepsy, is similarly observed in genetic seizure mutants: bangsenseless1 (bss1) and paralyticK1270T (paraK1270T). Exposure of bss1 to clinically-used antiepileptic drugs (phenytoin or gabapentin) significantly reduces synchrony. In this study we use the measure of synchronicity to evaluate the effectiveness of known and novel anticonvulsive compounds (antipain, isethionate, etopiside rapamycin and dipyramidole) to reduce seizure-like CNS activity. We further show that such compounds also reduce the Drosophila voltage-gated persistent Na+ current (INaP) in an identified motoneuron (aCC). Our combined assays provide a rapid and reliable method to screen unknown compounds for potential to function as anticonvulsants.

Complementary and alternative medicine use and nutrient intake among individuals with multiple sclerosis in the United States.

Individuals with multiple sclerosis (MS) often use complementary and alternative medicine (CAM). However, specific CAM therapies used within this population have not been thoroughly described, particularly the use of supplements, herbal remedies, and dietary modifications. The aim of this pilot study was to determine the prevalence of specific types of CAM used by adults with MS in the United States. Participants included adults who were diagnosed with MS at least 1 year prior to study enrollment. CAM use was measured using the CAM Supplement of the National Health Interview Survey, and nutrient intake was assessed using an Automated Self-Administered 24-h Recall. This study found that a majority (77 %, n = 27) of the sample used CAM within the past 12 months, the most prevalent type being vitamins/minerals (88.9 %, n = 24), nonvitamin, nonmineral, natural products (NP) (44.4 %, n = 12), relaxation techniques (33.3 %, n = 9), and special diets (29.6 %, n = 8). Regarding diet, median percent calories from fat (37 %) and saturated fat (12 %) were higher than current recommendations, while dietary fiber intake met only 87 % of the adequate intake. Participants following the Paleo (7.4 %, n = 2) diet did not meet the Estimated Average Requirement (EAR) for vitamins D and E, while those on the Swank diet (7.4 %, n = 2) were below the EAR for vitamins C, A, E, and folate. The results support previous findings that CAM therapies are commonly used by individuals with MS. Inadequate intakes of certain vitamins and minerals by those following the Swank and Paleo diet suggest these diets may be too restrictive, thus further research is warranted.