[show abstract][hide abstract] ABSTRACT: Innovative molecular and genetic techniques have recently led to the identification of genetically defined populations of ipsilaterally projecting excitatory interneurons with probable functions in the rhythm-generating kernel of the central pattern generators (CPGs). The role of interneuronal populations in specific motor function is determined by their synaptic inputs, intrinsic properties, and target neurons. In this review we examine whether Hb9-expressing interneurons (Hb9 INs) fulfill a set of criteria that are the hallmarks of rhythm generators in the locomotor circuitry. Induced locomotor-like activity in this distinct population of ventral interneurons is in phase with bursts of motor activity, raising the possibility that they are part of the locomotor generator. To increase our understanding of the integrative function of Hb9 INs in the locomotor CPG, we investigated the cellular mechanisms underlying their rhythmic activity and examined the properties of synaptic inputs from low-threshold afferents and possible synaptic contacts with segmental motoneurons. Our findings suggest that the rhythmogenic Hb9 INs are integral components of the sensorimotor circuitry that regulate locomotor-like activity in the spinal cord.
Annals of the New York Academy of Sciences 06/2010; 1198:72-84. · 4.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: The central pattern generator can generate locomotor-like rhythmic activity in the spinal cord in the absence of descending and peripheral inputs, but the motor pattern is regulated by feedback from peripheral sensory inputs that adjust motor outputs to external stimuli. To elucidate the possible role of Hb9-expressing interneurons (Hb9 INs) in the locomotor circuitry, we investigated whether their induced oscillatory activity is modulated by low-threshold afferents in the isolated spinal cords of neonatal Hb9:eGFP transgenic mice. Low-intensity stimulation of segmental afferents generated short-latency, monosynaptic excitatory responses in 62% of Hb9 INs. These were associated with longer-latency (approximately 13 ms) excitatory postsynaptic currents that were evoked in all Hb9 INs, probably by slow conducting afferents that synapse directly onto them. Concomitant morphological analysis confirmed that afferent axons with immunoreactive expression of vesicular glutamate transporter-1 and parvalbumin, presumably from primary afferents, contacted somata and dendrites of all Hb9 INs. Most of the putative synaptic contacts were on distal dendrites that extended to an area with profuse afferent projections. We next examined whether low-threshold afferents in upper (flexor-related) and lower (extensor-related) lumbar segments altered the timing of neurochemically induced locomotor-like rhythms in Hb9 INs and motoneurons. Excitation of flexor-related afferents during the flexor phase delayed the onset of subsequent cycles in both Hb9 INs and segmental motoneurons while maintaining the phase relationship between them. The in-phase correlation between voltage oscillations in Hb9 INs and motor bursts also persisted during the two- to threefold increase in cycle period triggered by extensor-related afferents. Our findings that low-threshold, presumably muscle afferents, synapse directly onto these interneurons and perturb their induced locomotor-like membrane oscillations in a pattern that remains phase-locked with motor bursts support the hypothesis that Hb9 INs are part of the sensorimotor circuitry that regulates the pattern of locomotor rhythms in the isolated cord.
Journal of Neurophysiology 06/2010; 103(6):3407-23. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Neurochemically induced membrane voltage oscillations and firing episodes in spinal excitatory interneurons expressing the HB9 protein (Hb9 INs) are synchronous with locomotor-like rhythmic motor outputs, suggesting that they contribute to the excitatory drive of motoneurons during locomotion. Similar to central pattern generator neurons in other systems, Hb9 INs are interconnected via electrical coupling, and their rhythmic activity does not depend on fast glutamatergic synaptic transmission. The primary objective of this study was to determine the contribution of fast excitatory and inhibitory synaptic transmission and subthreshold voltage-dependent currents to the induced membrane oscillations in Hb9 INs in the postnatal mouse spinal cord. The non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced the amplitude of voltage oscillations but did not alter their frequency. CNQX suppressed rhythmic motor activity. Blocking glycine and GABAA receptor-mediated inhibitory synapses as well as cholinergic transmission did not change the properties of CNQX-resistant membrane oscillations. However, disinhibition triggered new episodes of slow motor bursting that were not correlated with induced locomotor-like rhythms in Hb9 INs. Our observations indicated that fast excitatory and inhibitory synaptic inputs did not control the frequency of induced rhythmic activity in Hb9 INs. We next examined the contribution of persistent sodium current (INaP) to subthreshold membrane oscillations in the absence of primary glutamatergic, GABAergic and glycinergic synaptic drive to Hb9 INs. Low concentrations of riluzole that blocked the slow-inactivating component of sodium current gradually suppressed the amplitude and reduced the frequency of voltage oscillations. Our finding that INaP regulates locomotor-related rhythmic activity in Hb9 INs independently of primary synaptic transmission supports the concept that these neurons constitute an integral component of the rhythmogenic locomotor network in the mouse spinal cord.
Journal of Neurophysiology 08/2008; 100(4):2254-64. · 3.30 Impact Factor