Motorunits,consistingofasinglemotorneuronandthesetofmusclefiberstheyinnervate,arethefinalcommon output of the motor commands. The connectionbetween the motorneuronand its muscle fibers is extremely reliable,makingmotorneuronstheonlycellsinthecentralnervoussystem(CNS)whoseoutputcanbereadily measuredandlinkedtotheirfunctionaloutput(i.e.forcegeneration).Manymotorunitpoolsmustaccommodate a rich diversityof motor behaviors, including rhythmic repetitive behaviors, volitional movements, and postural maintenance.Ouroverallgoalistoinvestigatethemechanismsgoverningtheneuromotorcontrolofbehavioral diversity. A multiplicity of motor neuron input-output functions has been observed in non-human animal electrophysiologicalstudies,withmotorneuronsbehaviorasoscillators,variablegainamplifiers,orintegrators. Our overall concept is that these motor neuron electrical states are adaptations to perform distinct functional behaviors. To understand the relationship between these electrical states and motor behaviors, our goal is to usestateofthearthigh-densitysurfaceelectromyography(EMG)arraystorecordmotorunitdischargepatterns from several chest wall muscles that are active during breathing, volitional movements, and postural maintenance. These discharge patterns contain information about both thedescendingdrive to motor neurons aswellastheirintrinsicproperties.Oneimportantfactoristheprofoundeffectneuromodulationcanhaveonthe intrinsic excitability of motor neurons. Based on electrophysiological studies, neuromodulatory inputs seem to be much more important for posture and volition than for breathing and other lower-force rhythmic activities, which are instead primarily driven by glutamatergic activation of NMDA receptors. A common feature of high levels of neuromodulation is hysteresis in the onset and offset frequency of motor units. On the other hand, NMDA receptorsare self-inactivating and thus are unlikelyto generate discharge ratehysteresis.
In Aim 1, we willusehigh-densitysurfaceEMGarraystorecordandsubsequentlydiscriminatemotorunitdischargepatterns from four chest wall muscles in humans during automatic breathing, volitional breathing, and sustained trunk rotations.Wehypothesizethatdischargeratehysteresiswillbepositiveduringvolitionalbreathingandsustained trunk rotations, and nil or negative during automatic breathing. These experiments will identify motor unit discharge pattern signatures, such as discharge rate hysteresis, during distinct functional behaviors that correspond to motor neuron electrical states.
In Aim 2, we will employ pharmacological manipulations to determine potential mechanisms underlying motor control of breathing and other behaviors. Our proposed studieswillclarifymotorneuronadaptationstosatisfydiversebehavioraldemandsandprovideabasisforbetter diagnostic assessments of neuromuscular function in healthy and impaired states. These findings may help improve clinical diagnostic assessments of neuromuscular impairments and subsequently identify better therapeutictargetstoimprovefunctionduringspecificmotorbehavior.
Motor neurons are the only cells in the central nervous system whose discharge patterns can be routinely measured in humansand related directly tofunctional output.Ourgoal is touse state-of-the-art multielectrode surface EMG arrays to noninvasively decompose motor unit discharge patterns during distinct functional behaviors in humans and during pharmacological perturbations in cats. Our proposed studies will clarify the mechanisms underlying the neuromotor control of behavioral diversity and enhance understanding of both healthyandimpairedneuromuscularstates.
