Functional plasticity of glutamatergic neurons of medullary reticular nuclei after spinal cord injury in mice.

Spinal cord injury disrupts the descending command from the brain and causes a range of motor deficits. Here, we use optogenetic tools to investigate the functional plasticity of the glutamatergic reticulospinal drive of the medullary reticular formation after a lateral thoracic hemisection in female mice. Sites evoking stronger excitatory descending drive in intact conditions are the most impaired after injury, whereas those associated with a weaker drive are potentiated.

Functional contribution of mesencephalic locomotor region nuclei to locomotor recovery after spinal cord injury.

Spinal cord injury (SCI) results in a disruption of information between the brain and the spinal circuit. Electrical stimulation of the mesencephalic locomotor region (MLR) can promote locomotor recovery in acute and chronic SCI rodent models. Although clinical trials are currently under way, there is still debate about the organization of this supraspinal center and which anatomic correlate of the MLR should be targeted to promote recovery.

Heterozygous Mutant Mice Have a Subtle Locomotor Phenotype.

Axon guidance receptors such as deleted in colorectal cancer (DCC) contribute to the normal formation of neural circuits, and their mutations can be associated with neural defects. In humans, heterozygous mutations in have been linked to congenital mirror movements, which are involuntary movements on one side of the body that mirror voluntary movements of the opposite side. In mice, obvious hopping phenotypes have been reported for bi-allelic mutations, while heterozygous mutants have not been closely examined.

Role of DSCAM in the Development of Neural Control of Movement and Locomotion.

Locomotion results in an alternance of flexor and extensor muscles between left and right limbs generated by motoneurons that are controlled by the spinal interneuronal circuit. This spinal locomotor circuit is modulated by sensory afferents, which relay proprioceptive and cutaneous inputs that inform the spatial position of limbs in space and potential contacts with our environment respectively, but also by supraspinal descending commands of the brain that allow us to navigate in complex environments, avoid obstacles, chase prey, or flee predators. Although signaling pathways are important in the establishment and maintenance of motor circuits, the role of DSCAM, a cell adherence molecule associated with Down syndrome, has only recently been investigated in the context of motor control and locomotion in the rodent.

Glutamatergic neurons of the gigantocellular reticular nucleus shape locomotor pattern and rhythm in the freely behaving mouse.

Because of their intermediate position between supraspinal locomotor centers and spinal circuits, gigantocellular reticular nucleus (GRN) neurons play a key role in motor command. However, the functional contribution of glutamatergic GRN neurons in initiating, maintaining, and stopping locomotion is still unclear. Combining electromyographic recordings with optogenetic manipulations in freely behaving mice, we investigate the functional contribution of glutamatergic brainstem neurons of the GRN to motor and locomotor activity.

DSCAM Mutation Impairs Motor Cortex Network Dynamic and Voluntary Motor Functions.

While it is well known that netrin-1 and its receptors UNC5 and UNC40 family members are involved in the normal establishment of the motor cortex and its corticospinal tract, less is known about its other receptor Down syndrome cell adherence molecule (DSCAM). DSCAM is expressed in the developing motor cortex, regulates axonal outgrowth of cortical neurons, and its mutation impairs the dendritic arborization of cortical neurons, thus suggesting that it might be involved in the normal development and functioning of the motor cortex. In comparison to WT littermates, DSCAM2J mutant mice slipped and misplaced their paw while walking on the rungs of a horizontal ladder, and exhibited more difficulties in stepping over an obstacle while walking at slow speed.

Distinct Contributions of Mesencephalic Locomotor Region Nuclei to Locomotor Control in the Freely Behaving Mouse.

The mesencephalic locomotor region (MLR) has been initially identified as a supraspinal center capable of initiating and modulating locomotion. Whereas its functional contribution to locomotion has been widely documented throughout the phylogeny from the lamprey to humans, there is still debate about its exact organization. Combining kinematic and electrophysiological recordings in mouse genetics, our study reveals that glutamatergic neurons of the cuneiform nucleus initiate locomotion and induce running gaits, whereas glutamatergic and cholinergic neurons of the pedunculopontine nucleus modulate locomotor pattern and rhythm, contributing to slow-walking gaits.

Lessons Learned from Protective Immune Responses to Optimize Vaccines against Cryptosporidiosis.

In developing countries, cryptosporidiosis causes moderate-to-severe diarrhea and kills thousands of infants and toddlers annually. Drinking and recreational water contaminated with spp. oocysts has led to waterborne outbreaks in developed countries.

Age- and speed-dependent modulation of gaits in DSCAM mutant mice.

Gaits depend on the interplay between distributed spinal neural networks, termed central pattern generators, generating rhythmic and coordinated movements, primary afferents, and descending supraspinal inputs. Recent studies demonstrated that the mouse displays a rich repertoire of gaits. Changes in gaits occur in mutant mice lacking particular neurons or molecular signaling pathways implicated in the normal establishment of these neural networks.

Motor hypertonia and lack of locomotor coordination in mutant mice lacking DSCAM.

Down syndrome cell adherence molecule (DSCAM) contributes to the normal establishment and maintenance of neural circuits. Whereas there is abundant literature regarding the role of DSCAM in the neural patterning of the mammalian retina, less is known about motor circuits. Recently, DSCAM mutation has been shown to impair bilateral motor coordination during respiration, thus causing death at birth.

Role of DSCAM in the development of the spinal locomotor and sensorimotor circuits.

Locomotion is controlled by spinal circuits that generate rhythm and coordinate left-right and flexor-extensor motoneuronal activities. The outputs of motoneurons and spinal interneuronal circuits are shaped by sensory feedback, relaying peripheral signals that are critical to the locomotor and postural control. Several studies in invertebrates and vertebrates have argued that the Down syndrome cell adhesion molecule (DSCAM) would play an important role in the normal development of neural circuits through cell spacing and targeting, axonal and dendritic branching, and synapse establishment and maintenance.

Neocortical inhibitory activities and long-range afferents contribute to the synchronous onset of silent states of the neocortical slow oscillation.

During slow-wave sleep, neurons of the thalamocortical network are engaged in a slow oscillation (<1 Hz), which consists of an alternation between the active and the silent states. Several studies have provided insights on the transition from the silent, which are essentially periods of disfacilitation, to the active states. However, the conditions leading to the synchronous onset of the silent state remain elusive.

The impact of cortical deafferentation on the neocortical slow oscillation.

Slow oscillation is the main brain rhythm observed during deep sleep in mammals. Although several studies have demonstrated its neocortical origin, the extent of the thalamic contribution is still a matter of discussion. Using electrophysiological recordings in vivo on cats and computational modeling, we found that the local thalamic inactivation or the complete isolation of the neocortical slabs maintained within the brain dramatically reduced the expression of slow and fast oscillations in affected cortical areas.

Corticothalamic feedback controls sleep spindle duration in vivo.

Spindle oscillations are commonly observed during stage 2 of non-rapid eye movement sleep. During sleep spindles, the cerebral cortex and thalamus interact through feedback connections. Both initiation and termination of spindle oscillations are thought to originate in the thalamus based on thalamic recordings and computational models, although some in vivo results suggest otherwise.

Distribution of the neuronal gap junction protein Connexin36 in the spinal cord enlargements of developing and adult opossums, Monodelphis domestica.

We use opossums Monodelphis domestica to study the development of mammalian motor systems. The immature forelimbs of the newborn perform rhythmic and alternating movements that are likely under spinal control. The hindlimbs start moving in the second week.