Biology subjects

Bhumbra, G. S.

Publications and source records attributed to Bhumbra, G. S..

6 recordsLinked to original sources

bioRxiv2025

Evidence of spinal cord comparator modules for rapid corrections of movements

Successful movement requires continuous adjustments in response to changes in internal and external environments. To do so, neural circuits continuously compare efference copies of motor commands with sensory feedback to respond to sensory prediction errors. Some responses need to be very fast, indicating that they likely occur within spinal cord circuits. Here, we describe spinal cord circuits involving dI3 neurons, showing that they receive multimodal sensory inputs and direct efferent copies from both Renshaw cells and motor neurons. We further show that they form connections to motor pools. Reducing dI3 neuronal activity diminished stumbling responses, as did disrupting Renshaw cell circuits, providing evidence for a comparator role of dI3 neurons for online corrections. Together, our findings reveal a pivotal role for dI3 neurons functioning as comparators of efference copies and external sensory feedback to mediate rapid corrections of ongoing movements.

neuroscience↗

bioRxiv2024

Spinal microcircuits go through multiphasic homeostatic compensations in a mouse model of motoneuron degeneration

In many neurological conditions, early-stage neural circuit adaption can preserve relatively normal behaviour. In some diseases, spinal motoneurons progressively degenerate yet movement is initially preserved. We therefore investigated whether these neurons and associated microcircuits adapt in a mouse model of progressive motoneuron degeneration. Using a combination of in vitro and in vivo electrophysiology and super-resolution microscopy, we found that, early in the disease, neurotransmission in a key pre-motor circuit, the recurrent inhibition mediated by Renshaw cells, is reduced by half due to impaired quantal size associated with decreased glycine receptor density. This impairment is specific, and not a widespread feature of spinal inhibitory circuits. Furthermore, it recovers at later stages of disease. Additionally, an increased probability of release from proprioceptive afferents leads to increased monosynaptic excitation of motoneurons. We reveal that in motoneuron degenerative conditions, spinal microcircuits undergo specific multiphasic homeostatic compensations that may contribute to preservation of force output.

neuroscience↗

bioRxiv2021

Spinal neurons innervating multiple local and distant motor pools

Motor neurons control muscle contractions, and their recruitment by premotor circuits is tuned to produce accurate motor behaviours. To understand how these circuits coordinate movement across and between joints, it is necessary to understand whether spinal neurons pre-synaptic to motor pools, project to more than one motor neuron population. Here, we used modified rabies virus tracing in mice to investigate premotor INs projecting to synergist flexor or extensor motor neurons, as well as those projecting to antagonist pairs of muscles controlling the ankle joint. We show that similar proportions of premotor neurons diverge to agonist and antagonist motor pools. Divergent premotor neurons were seen throughout the spinal cord, with decreasing numbers but increasing proportion with distance from the hindlimb enlargement. In the cervical cord, divergent long descending propriospinal neurons were found in contralateral lamina VIII, had large somata, were excitatory, projected to both lumbar and cervical motoneurons, and were at least in part of the V0 class. We conclude that distributed spinal premotor neurons coordinate activity across multiple motor pools and that there are spinal neurons mediating co-contraction of antagonist muscles.

neuroscience↗

bioRxiv2021

On the distribution of spinal premotor interneurons

Elaborate behaviours are produced by tightly controlled flexor-extensor motor neuron activation patterns. Motor neurons are regulated by a network of interneurons within the spinal cord, but the computational processes involved in motor control are not fully understood. The neuroanatomical arrangement of motor and premotor neurons into topographic patterns related to their controlled muscles is thought to facilitate how information is processed by spinal circuits. Rabies retrograde monosynaptic tracing has been used to label premotor interneurons innervating specific motor neuron pools, with previous studies reporting topographic mediolateral positional biases in flexor and extensor premotor interneurons. To more precisely define how premotor interneurons contacting specific motor pools are organized we used multiple complementary viral-tracing approaches to minimize systematic biases associated with each method. Contrary to expectations, we found that premotor interneurons contacting motor pools controlling flexion and extension of the ankle are highly intermingled rather than segregated into specific domains like motor neurons. Thus, premotor spinal neurons controlling different muscles process motor instructions in the absence of clear spatial patterns among the flexor-extensor circuit components. The paper can be downloaded in executable format as a MATLAB live script from https://github.com/marcobeato/Spinal_premotor_interneurons_controlling_antagonistic_muscles_are_spatially_intermingled, where all the data are available An R version of the executable paper is available at https://mybinder.org/v2/gh/rronzano/Spinal_premotor_interneurons_controlling_antagonistic_muscles_are_spatially_intermingled.git/HEAD?urlpath=rstudio

neuroscience↗

bioRxiv2018

Strong preference for autaptic self-connectivity of neocortical PV interneurons entrains them to γ-oscillations

Parvalbumin (PV) positive interneurons modulate cortical activity through highly specialized connectivity patterns onto excitatory pyramidal neurons (PNs) and other inhibitory cells. PV cells are auto-connected through powerful autapses, but the contribution of this form of fast disinhibition to cortical function is unknown. We found that autaptic transmission represents the most powerful input of PV cells in neocortical Layer V. Autaptic strength was greater than synaptic strength onto PNs as result of a larger quantal size, whereas autaptic and heterosynaptic PV-PV synapses differed in the number of release sites. Overall, single-axon autaptic transmission contributed to ~40% of the total perisomatic inhibition that PV interneurons received. The strength of autaptic transmission modulated the coupling of PV-cell firing with optogenetically-induced {gamma}-oscillations preventing high frequency bursts of spikes. Autaptic self-inhibition represents an exceptionally large and fast disinhibitory mechanism to synchronize the output of PV cells during cognitive-relevant cortical network activity.

neuroscience↗

bioRxiv2017

Recurrent excitation between motoneurones propagates across segments and is purely glutamatergic

Spinal motoneurones constitute the final output for the execution of motor tasks. In addition to innervating muscles, motoneurones project excitatory collateral connections to Renshaw cells and other motoneurones, but the latter have received little attention. We show that motoneurones receive strong synaptic input from other motoneurones throughout development and into maturity with fast type motoneurones systematically receiving greater recurrent excitation than slow type motoneurones. Optical recordings show that activation of motoneurones in one spinal segment can propagate to adjacent segments even in the presence of intact recurrent inhibition. Quite remarkably, while it is known that transmission at the neuromuscular junction is purely cholinergic and Renshaw cells are excited through both acetylcholine and glutamate receptors, here we show that neurotransmission between motoneurones is purely glutamatergic indicating that synaptic transmission systems are differentiated at different post-synaptic targets of motoneurones.

neuroscience↗