Imagined gait modulates neuronal network dynamics in the human pedunculopontine nucleus

The pedunculopontine nucleus (PPN) is a part of the mesencephalic locomotor region and is thought to be important for the initiation and maintenance of gait. Lesions of the PPN induce gait deficits, and the PPN has therefore emerged as a target for deep brain stimulation for the control of gait and postural disability. However, the role of the PPN in gait control is not understood. Using extracellular single-unit recordings in awake patients, we found that neurons in the PPN discharged as synchronous functional networks whose activity was phase locked to alpha oscillations. Neurons in the PPN responded to limb movement and imagined gait by dynamically changing network activity and decreasing alpha phase locking. Our results indicate that different synchronous networks are activated during initial motor planning and actual motion, and suggest that changes in gait initiation in Parkinson's disease may result from disrupted network activity in the PPN

Postsynaptic nigrostriatal dopamine receptors and their role in movement regulation

The article presents the hypothesis that nigrostriatal dopamine may regulate movement by modulation of tone and contraction in skeletal muscles through a concentration-dependent influence on the postsynaptic D1 and D2 receptors on the follow manner: nigrostriatal axons innervate both receptor types within the striatal locus somatotopically responsible for motor control in agonist/antagonist muscle pair around a given joint. D1 receptors interact with lower and D2 receptors with higher dopamine concentrations. Synaptic dopamine concentration increases immediately before movement starts. We hypothesize that increasing dopamine concentrations stimulate first the D1 receptors and reduce muscle tone in the antagonist muscle and than stimulate D2 receptors and induce contraction in the agonist muscle. The preceded muscle tone reduction in the antagonist muscle eases the efficient contraction of the agonist. Our hypothesis is applicable for an explanation of physiological movement regulation, different forms of movement pathology and therapeutic drug effects. Further, this hypothesis provides a theoretical basis for experimental investigation of dopaminergic motor control and development of new strategies for treatment of movement disorders

Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. © 2010 Macmillan Publishers Limited. All rights reserved

Locomotor speed control circuits in the caudal brainstem

Locomotion is a universal behaviour that provides animals with the ability to move between places. Classical experiments have used electrical microstimulation to identify brain regions that promote locomotion, but the identity of neurons that act as key intermediaries between higher motor planning centres and executive circuits in the spinal cord has remained controversial. Here we show that the mouse caudal brainstem encompasses functionally heterogeneous neuronal subpopulations that have differential effects on locomotion. These subpopulations are distinguishable by location, neurotransmitter identity and connectivity. Notably, glutamatergic neurons within the lateral paragigantocellular nucleus (LPGi), a small subregion in the caudal brainstem, are essential to support high-speed locomotion, and can positively tune locomotor speed through inputs from glutamatergic neurons of the upstream midbrain locomotor region. By contrast, glycinergic inhibitory neurons can induce different forms of behavioural arrest mapping onto distinct caudal brainstem regions. Anatomically, descending pathways of glutamatergic and glycinergic LPGi subpopulations communicate with distinct effector circuits in the spinal cord. Our results reveal that behaviourally opposing locomotor functions in the caudal brainstem were historically masked by the unexposed diversity of intermingled neuronal subpopulations. We demonstrate how specific brainstem neuron populations represent essential substrates to implement key parameters in the execution of motor programs

Role of orexin in central regulation of gastrointestinal functions

The original publication is available at springerlink.com authorOrexins are neuropeptides that are localized in neurons within the lateral hypothalamus and regulate feeding behavior. The lateral hypothalamus plays an important role in not only feeding but the central regulation of gut function. Along this line, accumulating evidence have shown that orexins acts in the central nervous system to regulate gastrointestinal functions. The purpose of this review is to summarize recent relevant findings on brain orexins and a digestive system, and discuss the pathophysiological roles of the peptides. Centrally administered orexin or endogenously released orexin in the brain potently stimulates gastric acid secretion in rats. The vagal cholinergic pathway is involved in the orexin-induced stimulation of acid secretion. Considering its stimulatory action on feeding, it should be hypothesized that orexin in the brain is a candidate mediator of cephalic phase gastric secretion. In addition, brain orexin may be involved in the development of depression and functional gastrointestinal disorders which are frequently accompanied with the inhibition of gut function, because lack of orexin action might induce the inhibition of gastric physiology and evoke depressive state. These evidence suggest that orexin in the brain would be a possible molecular target for the treatment of functional gastrointestinal disorders

Nigral GABAergic inhibition upon mesencephalic dopaminergic cell groups in rats

The definitive version is available at www.3.interscience.wiley.comSynaptic inhibition from the substantia nigra pars reticulata (SNr) to the mesencephalic dopaminergic neurons, which was mediated by gamma (gamma)-amino-butyric acid (GABA), was investigated in a midbrain slice preparation of Wistar rats. Whole-cell patch-clamp recordings were used to record synaptic potentials/currents from the dopaminergic neurons (n = 93) located in the retrorubral field (n = 22), the substantia nigra pars compacta (n = 47) and the ventral tegmental area (n = 24). In the presence of ionotropic glutamate receptor antagonists electrical stimulation of the SNr induced inhibitory postsynaptic potentials (IPSPs) and/or currents (IPSCs) in 83 neurons. The IPSPs/IPSCs were comprised early and late components. The early IPSPs/IPSCs were mediated by chloride currents through GABA(A) receptors. The late IPSPs/IPSCs were mediated by potassium currents through GABA(B) receptors. Both GABA(A)- and GABA(B)-IPSPs were amplified by repetitive stimuli with frequencies between 25 and 200 Hz. This frequency range covers the firing frequencies of SNr neurons in vivo. It was observed that an application of a GABA(B) receptor antagonist increased the amplitude of the GABA(A)-IPSPs. The amplification was followed by a rebound depolarization that induced transient firing of dopaminergic neurons. These properties of the IPSPs were common in all of the three dopaminergic nuclei. These results suggest that postsynaptic GABA(A)- and GABA(B)-inhibition contribute to transient and persistent alternations of the excitability of dopaminergic neurons, respectively. These postsynaptic mechanisms may be, in turn, regulated by presynaptic GABA(B)-inhibition. Nigral GABAergic input may provide the temporospatial regulation of the background excitability of mesencephalic dopaminergic systems

Medullary reticulospinal tract mediating a generalized motor inhibition in cats: III. Functional organization of spinal interneurons in the lower lumbar segments

http://dx.doi.org/10.1016/S0306-4522(03)00542-6The previous report of intracellular recording of hindlimb motoneurons in decerebrate cats [[Delwaide, 2001] 511] has suggested that the following mechanisms are involved in a generalized motor inhibition induced by stimulating the medullary reticular formation. First, the motor inhibition, which was prominent in the late latency (30–80 ms), can be ascribed to the inhibitory effects in parallel to motoneurons and to interneuronal transmission in reflex pathways. Second, both a group of interneurons receiving inhibition from flexor reflex afferents and a group of Ib interneurons mediate the late inhibitory effects upon the motoneurons. To substantiate the above mechanisms of motor inhibition we examined the medullary stimulus effects upon intracellular (n=55) and extracellular (n=136) activity of spinal interneurons recorded from the lower lumbar segments (L6–L7). Single pulses or stimulus trains (1–3) pulses, with a duration of 0.2 ms and intensity of 20–50 μA) applied to the medullary nucleus reticularis gigantocellularis evoked a mixture of excitatory and inhibitory effects with early (30 ms) latencies. The medullary stimulation excited 55 interneurons (28.8%) with a late latency. Thirty-nine of the cells, which included 10 Ib interneurons, were inhibited by volleys in flexor reflex afferents (FRAs). These cells were mainly located in lamina VII of Rexed. On the other hand, the late inhibitory effects were observed in 67 interneurons (35.1%), which included cells mediating reciprocal Ia inhibition, non-reciprocal group I (Ib) inhibition, recurrent inhibition and flexion reflexes. Intracellular recording revealed that the late inhibitory effects were due to inhibitory postsynaptic potentials with a peak latency of about 50 ms and a duration of 50–60 ms. The inhibitory effects were attenuated by volleys in FRAs. Neither excitatory nor inhibitory effects with a late latency were observed in 69 (36.1%) cells which were located in the intermediate region and dorsal horn. These results suggest the presence of a functional organization of the spinal cord with respect to the production of the generalized motor inhibition. Lamina VII interneurons that receive inhibition from volleys in FRAs possibly mediate the postsynaptic inhibition from the medullary reticular formation in parallel to motoneurons and to interneurons in reflex pathways