Equilibrium potential of GABA(A) current and implications for rebound burst firing in rat subthalamic neurons in vitro.
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Reciprocally connected glutamatergic subthalamic and GABAergic globus pallidus neurons have recently been proposed to act as a generator of low-frequency oscillatory activity in Parkinson's disease. To determine whether GABA(A) receptor-mediated synaptic potentials could theoretically generate rebound burst firing in subthalamic neurons, a feature that is central to the proposed oscillatory mechanism, we determined the equilibrium potential of GABA(A) current (E(GABA(A))) and the degree of hyperpolarization required for rebound firing using perforated-patch recording. In the majority of neurons that fired rebounds, E(GABA(A)) was equal to or more hyperpolarized than the hyperpolarization required for rebound burst firing. These data suggest that synchronous activity of pallidal inputs could underlie rhythmic bursting activity of subthalamic neurons in Parkinson's disease. (+info)
Identification of the anterior nucleus of the ansa lenticularis in birds as the homolog of the mammalian subthalamic nucleus.
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In mammals, the subthalamic nucleus (STN) is a glutamatergic diencephalic cell group that develops in the caudal hypothalamus and migrates to a position above the cerebral peduncle. By its input from the external pallidal segment and projection to the internal pallidal segment, STN plays a critical role in basal ganglia functions. Although the basal ganglia in birds is well developed, possesses the same major neuron types as in mammals, and plays a role in movement control similar to that in mammals, it has been uncertain whether birds possess an STN. We report here evidence indicating that the so-called anterior nucleus of the ansa lenticularis (ALa) is the avian homolog of mammalian STN. First, the avian ALa too develops within the mammillary hypothalamic area and migrates to a position adjacent to the cerebral peduncle. Second, ALa specifically receives input from dorsal pallidal neurons that receive input from enkephalinergic striatal neurons, as is true of STN. Third, ALa projects back to avian dorsal pallidum, as also the case for STN in mammals. Fourth, the neurons of ALa contain glutamate, and the target neurons of ALa in dorsal pallidum possess AMPA-type glutamate receptor profiles resembling those of mammalian pallidal neurons. Fifth, unilateral lesions of ALa yield behavioral disturbances and movement asymmetries resembling those observed in mammals after STN lesions. These various findings indicate that ALa is the avian STN, and they suggest that the output circuitry of the basal ganglia for motor control is similar in birds and mammals. (+info)
Neurons of a limited subthalamic area mediate elevations in cortical cerebral blood flow evoked by hypoxia and excitation of neurons of the rostral ventrolateral medulla.
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Sympathoexcitatory reticulospinal neurons of the rostral ventrolateral medulla (RVLM) are oxygen detectors excited by hypoxia to globally elevate regional cerebral blood flow (rCBF). The projection, which accounts for >50% of hypoxic cerebral vasodilation, relays through the medullary vasodilator area (MCVA). However, there are no direct cortical projections from the RVLM/MCVA, suggesting a relay that diffusely innervates cortex and possibly originates in thalamic nuclei. Systematic mapping by electrical microstimulation of the thalamus and subthalamus revealed that elevations in rCBF were elicited only from a limited area, which encompassed medial pole of zona incerta, Forel's field, and prerubral zone. Stimulation (10 sec train) at an active site increased rCBF by 25 +/- 6%. Excitation of local neurons with kainic acid mimicked effects of electrical stimulation by increasing rCBF. Stimulation of the subthalamic cerebrovasodilator area (SVA) with single pulses (0.5 msec; 80 microA) triggered cortical EEG burst-CBF wave complexes with latency 24 +/- 5 msec, which were similar in shape to complexes evoked from the MCVA. Selective bilateral lesioning of the SVA neurons (ibotenic acid, 2 microg, 200 nl) blocked the vasodilation elicited from the MCVA and attenuated hypoxic cerebrovasodilation by 52 +/- 12% (p < 0.05), whereas hypercarbic vasodilation remained preserved. Lesioning of the vasodilator site in the basal forebrain failed to modify SVA-evoked rCBF increase. We conclude that (1) excitation of intrinsic neurons of functionally restricted region of subthalamus elevates rCBF, (2) these neurons relay signals from the MCVA, which elevate rCBF in response to hypoxia, and (3) the SVA is a functionally important site conveying vasodilator signal from the medulla to the telencephalon. (+info)
Segregation and convergence of information flow through the cortico-subthalamic pathways.
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Cortico-basal ganglia circuits are organized in parallel channels. Information flow from functionally distinct cortical areas remains segregated within the striatum and through its direct projections to basal ganglia output structures. Whether such a segregation is maintained in trans-subthalamic circuits is still questioned. The effects of electrical stimulation of prefrontal, motor, and auditory cortex were analyzed in the subthalamic nucleus as well as in the striatum of anesthetized rats. In the striatum, cells (n = 300) presenting an excitatory response to stimulation of these cortical areas were located in distinct striatal territories, and none of the cells responded to two cortical stimulation sites. In the subthalamic nucleus, both prefrontal and motor cortex stimulations induced early and late excitatory responses as a result of activation of the direct cortico-subthalamic pathway and of the indirect cortico-striato-pallido-subthalamic pathway, respectively. Stimulation of the auditory cortex, which does not send direct projection to the subthalamic nucleus, induced only late excitatory responses. Among the subthalamic responding cells (n = 441), a few received both prefrontal and motor cortex (n = 19) or prefrontal and auditory cortex (n = 10) excitatory inputs, whereas a larger number of cells were activated from both motor and auditory cortices (n = 48). The data indicate that the segregation of cortical information flow originating from prefrontal, motor, and auditory cortices that occurred in the striatum is only partly maintained in the subthalamic nucleus. It can be proposed that the existence of specific patterns of convergence of information flow from these functionally distinct cortical areas in the subthalamic nucleus allows interactions between parallel channels. (+info)
Spinal projections of the cat parvicellular red nucleus.
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Traditionally, the red nucleus of the cat is divided into two parts: a large-celled, magnocellular, division (RNm) and a small-celled, parvicellular, division (RNp). The RNm projects to the spinal cord and receives input from the cerebellar interpositus nucleus. The RNp projects to the inferior olive and receives input from the cerebellar dentate nucleus. In this report, we reexamine the connections of the red nucleus using the bidirectional tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP). Our findings demonstrate that the cat RNp has a large caudal and lateral region that projects to contralateral spinal cord and not to the inferior olive. The spinally projecting region of RNp receives input from the dentate nucleus and a lateral segment of anterior interpositus. Cervical projections from the red nucleus show a topography with the rostral portion of RNp favoring upper segments and the caudal portion of RNm favoring lower segments. The results show that dentate output can influence spinal activity without passing through the cerebral cortex. For the control of movements such as reaching and grasping, we suggest that RNp and dentate focus on the control of proximal limb musculature, whereas RNm and the anterior interpositus focus on the control of distal limb musculature. We also suggest that other species are likely to have a small-celled area of red nucleus projecting to the spinal cord. (+info)
Behavioral consequences of bicuculline injection in the subthalamic nucleus and the zona incerta in rat.
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The subthalamic nucleus (STN) plays a crucial role in basal ganglia functions and has been shown to be hyperactive in parkinsonian syndromes. The zona incerta (ZI), located dorsally to the STN, is also reported to be overactive after nigrostriatal denervation. In this study, we examined the behavioral consequences of an increased activity of the STN or the ZI in awake, freely moving rats. Unilateral microinjections of a GABA(A) receptor antagonist (bicuculline; 25, 50, and 100 microg/microl) were performed in the STN or in the ZI of rats, and locomotor activity, spontaneous behaviors, and the occurrence of abnormal movements were quantified. Microinjection of bicuculline (50 and 100 microg/microl) into the STN did not modify spontaneous locomotor activity, whereas it induced an increase in locomotion when injected into the ZI. Furthermore, when injected into the STN or ZI, these same doses of bicuculline produced changes in spontaneous behaviors (sniffing and grooming decreased whereas chewing and rearing increased) and the appearance of abnormal movements directed contralaterally to the injection side. Application of a lower dose of bicuculline (25 ng/microl) in the STN or ZI did not modify behavior. This study suggests that the subthalamic region including the ZI, and not the STN per se, might be involved in the induction of abnormal movements. In addition, these data suggest that the hyperactivity of neurons in this region may have different consequences in the normal state and in the pathological state. (+info)
Arcuate plan of chick midbrain development.
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In spinal cord and hindbrain development, neurons are generated as longitudinal cell columns aligned with the ventral and dorsal midlines. For rostral brain, however, the fundamental structure of early neuronal patterning remains poorly understood. We report here that, in the chick embryo, the ventral midbrain is remarkably regular in its cellular and molecular organization; it is arranged as a reiterative series of arcuate territories arrayed bilateral to the ventral midline. In the mantle layer of the ventral midbrain, an arcuate series of neuronal cell columns (midbrain arcs) is demonstrated by acetylcholinesterase histochemistry and gene expression for class III beta-tubulin, homeodomain transcription factors, and neurotransmitter synthetic enzymes. In the ventricular layer of midbrain progenitor cells, WNT and NOTCH ligand gene expression displays arcuate periodicities that form a tight three-dimensional registration with the arcs of the underlying mantle layer. Ventral midbrain arcuate patterning is even macroscopically visible, forming ridges along the ventricular surface. These observations establish that a single plan of arcuate organization governs the morphogenesis and cell-type specification of the ventral midbrain. Arcs are not restricted to the midbrain tegmentum but extend through the subthalamic tegmentum of the forebrain. Thus, the chick rostral brain, which is classically divided into midbrain and forebrain, can also be partitioned into the following: (1) a neuraxial region of arcs and (2) an anterodorsal cap that includes midbrain tectum and nonsubthalamic forebrain. We show that this partition of brain tissue is supported by the expression patterns of homologs of Drosophila gap genes. (+info)
Reducing the uncertainty: gating of peripheral inputs by zona incerta.
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Sensory inputs are relayed to the neocortex by "first-order" thalamic nuclei, the responses of which are determined by ascending inputs from peripheral receptors. In contrast, "higher-order" thalamic nuclei respond poorly to peripheral inputs, and their responses are thought to be determined by descending cortical inputs. We tested this hypothesis by recording from neurons in the higher-order somatosensory posterior medial (POm) nucleus of narcotized rats. As reported previously, POm neurons responded to whisker stimuli with long-latency (median, 27 msec) and low-magnitude responses, consistent with cortically driven responses. However, when we suppressed inhibitory inputs from the subthalamic nucleus zona incerta (ZI), POm responses were of significantly higher magnitude and shorter latency, with many POm neurons responding at latencies consistent with ascending driving inputs from trigeminal nuclei. Our data suggest that POm comprises two neuronal populations: one population is driven by both peripheral and cortical inputs, and the second population responds only to cortical inputs. These findings demonstrate that ZI gates peripheral inputs to POm, enabling it to function both as a first-order and higher-order nucleus. Because ZI innervates all higher-order nuclei, this gating mechanism may exert similar regulation of thalamic processing in other sensory systems. (+info)