Intrinsic brainstem circuits comprised of Chx10-expressing neurons contribute to reticulospinal output in mice

Glutamatergic reticulospinal neurons in the gigantocellular reticular nucleus (GRN) of the medullary reticular formation can function as command neurons, transmitting motor commands to spinal cord circuits to instruct movement. Recent advances in our understanding of this neuron-dense region have been facilitated by the discovery of expression of the transcriptional regulator, Chx10, in excitatory reticulospinal neurons. Here, we address the capacity of local circuitry in the GRN to contribute to reticulospinal output. We define two sub-populations of Chx10-expressing neurons in this region, based on distinct electrophysiological properties and somata size (small and large), and show that these populations correspond to local interneurons and reticulospinal neurons, respectively. Using focal release of caged glutamate combined with patch clamp recordings, we demonstrated that Chx10 neurons form microcircuits in which the Chx10 local interneurons project to and facilitate the firing of Chx10 reticulospinal neurons. We discuss the implications of these microcircuits in terms of movement selection

alpha-Motoneurons maintain biophysical heterogeneity in obesity and diabetes in Zucker rats

Small-diameter sensory dysfunction resulting from diabetes has received much attention in the literature, whereas the impact of diabetes on α-motoneurons (MN) has not. In addition, the chance of developing insulin resistance and diabetes is increased in obesity. No study has examined the impact of obesity or diabetes on the biophysical properties of MN. Lean Zucker rats and Zucker diabetic fatty (ZDF) rats were separated into lean, obese (ZDF fed standard chow), and diabetic (ZDF fed high-fat diet that led to diabetes) groups. Glass micropipettes recorded hindlimb MN properties from identified flexor and extensor MN. MN were separated within their groups on the basis of input conductance, which created high- and low-input conductance subpopulations for each. A significant shorter (20%) afterhyperpolarization half-decay (AHP1/2) was found in low-conductance MN for the diabetic group only, whereas AHP½ tended to be shorter in the obese group (19%). Significant positive correlations were found among rheobase and input conductance for both lean and obese animals. No differences were found between the groups for afterhyperpolarization amplitude (AHPamp), input conductance, rheobase, or any of the rhythmic firing properties (frequency-current slope and spike-frequency adaptation index). MN properties continue to be heterogeneous in obese and diabetic animals. Obesity does not seem to influence lumbar MN. Despite the resistance of MN to the impact of diabetes, the reduced AHP1/2 decay and the tendency for a reduction in AHPamp may be the first sign of change to MN function

Altered transcription of glutamatergic and glycinergic receptors in spinal cord dorsal horn following spinal cord transection is minimally affected by passive exercise of the hindlimbs

Gene expression is altered following a spinal transection (STx) in both motor and sensory systems. Exercise has been shown to influence gene expression in both systems post‐STx. Gene expression alterations have also been shown in the dorsal root ganglia and nociceptive laminae of the spinal cord following either an incomplete spinal cord injury (SCI) or a contusive SCI. However, the effect of STx and exercise on gene expression in spinal cord laminae I‐III has not fully been examined. Therefore, the purpose of this study was to determine whether gene expression in laminae I‐III is altered following STx and determine whether superimposed passive exercise of the hindlimbs would influence gene expression post‐STx in laminae I‐III. Laser capture microdissection was used to selectively harvest laminae I‐III of lumbar spinal cord sections, and quantitative RT‐PCR was used to examine relative expression of 23 selected genes in samples collected from control, STx and STx plus exercise rats. We demonstrate that post‐STx, gene expression for metabotropic glutamate receptors 1, 5 and 8 were up‐regulated, whereas ionotropic glutamatergic receptor (Glur2) and glycinergic subunit GLRA1 expression was down‐regulated. Daily exercise attenuated the down‐regulation of Glur2 gene expression in laminae I‐III. Our results demonstrate that in a STx model, gene expression is altered in laminae I‐III and that although passive exercise influences gene expression in both the motor and sensory systems, it had a minimal effect on gene expression in laminae I‐III post‐STx

Sub-populations of Spinal V3 Interneurons Form Focal Modules of Layered Pre-motor Microcircuits

Layering of neural circuits facilitates the separation of neurons with high spatial sensitivity from those that play integrative temporal roles. Although anatomical layers are readily identifiable in the brain, layering is not structurally obvious in the spinal cord. But computational studies of motor behaviors have led to the concept of layered processing in the spinal cord. It has been postulated that spinal V3 interneurons (INs) play multiple roles in locomotion, leading us to investigate whether they form layered microcircuits. Using patch-clamp recordings in combination with holographic glutamate uncaging, we demonstrate focal, layered modules, in which ventromedial V3 INs form synapses with one another and with ventrolateral V3 INs, which in turn form synapses with ipsilateral motoneurons. Motoneurons, in turn, provide recurrent excitatory, glutamatergic input to V3 INs. Thus, ventral V3 interneurons form layered microcircuits that could function to ensure well-timed, spatially specific movements

Caloric Restriction Suppresses Microglial Activation and Prevents Neuroapoptosis Following Cortical Injury in Rats

Traumatic brain injury (TBI) is a widespread cause of death and a major source of adult disability. Subsequent pathological events occurring in the brain after TBI, referred to as secondary injury, continue to damage surrounding tissue resulting in substantial neuronal loss. One of the hallmarks of the secondary injury process is microglial activation resulting in increased cytokine production. Notwithstanding that recent studies demonstrated that caloric restriction (CR) lasting several months prior to an acute TBI exhibits neuroprotective properties, understanding how exactly CR influences secondary injury is still unclear. The goal of the present study was to examine whether CR (50% of daily food intake for 3 months) alleviates the effects of secondary injury on neuronal loss following cortical stab injury (CSI). To this end, we examined the effects of CR on the microglial activation, tumor necrosis factor-α (TNF-α) and caspase-3 expression in the ipsilateral (injured) cortex of the adult rats during the recovery period (from 2 to 28 days) after injury. Our results demonstrate that CR prior to CSI suppresses microglial activation, induction of TNF-α and caspase-3, as well as neurodegeneration following injury. These results indicate that CR strongly attenuates the effects of secondary injury, thus suggesting that CR may increase the successful outcome following TBI

Case Studies in Neuroscience: Evidence of motor thalamus reorganization following bilateral forearm amputations

Following injury, functional improvement can result from central nervous system plasticity. Use-dependent plasticity of motor systems is evident, for example, in recovery of function resulting from rehabilitative interventions. Here, we present a single patient who underwent bilateral microelectrode-guided stereotactic implantation of deep brain stimulating leads for the treatment of essential tremor 52 yr following bilateral arm amputations. The tremor affected his upper extremities and had rendered him unable to perform fine motor tasks with his prostheses, significantly reducing his independence. We found a large territory of neurons in the ventral intermediate nucleus of his thalamus that responded to shoulder protraction, the movement that he used to control fine motor movements of his terminal hook prostheses. We propose that reorganization of this motor nucleus may have occurred secondary to a use-dependent gain of function in neurons that were previously involved in hand movement