Regulation of neurotrophin-3 expression by epithelial-mesenchymal interactions: the role of Wnt factors.
Neurotrophins regulate survival, axonal growth, and target innervation of sensory and other neurons. Neurotrophin-3 (NT-3) is expressed specifically in cells adjacent to extending axons of dorsal root ganglia neurons, and its absence results in loss of most of these neurons before their axons reach their targets. However, axons are not required for NT-3 expression in limbs; instead, local signals from ectoderm induce NT-3 expression in adjacent mesenchyme. Wnt factors expressed in limb ectoderm induce NT-3 in the underlying mesenchyme. Thus, epithelial-mesenchymal interactions mediated by Wnt factors control NT-3 expression and may regulate axonal growth and guidance. (+info)
Activity-dependent metaplasticity of inhibitory and excitatory synaptic transmission in the lamprey spinal cord locomotor network.
Paired intracellular recordings have been used to examine the activity-dependent plasticity and neuromodulator-induced metaplasticity of synaptic inputs from identified inhibitory and excitatory interneurons in the lamprey spinal cord. Trains of spikes at 5-20 Hz were used to mimic the frequency of spiking that occurs in network interneurons during NMDA or brainstem-evoked locomotor activity. Inputs from inhibitory and excitatory interneurons exhibited similar activity-dependent changes, with synaptic depression developing during the spike train. The level of depression reached was greater with lower stimulation frequencies. Significant activity-dependent depression of inputs from excitatory interneurons and inhibitory crossed caudal interneurons, which are central elements in the patterning of network activity, usually developed between the fifth and tenth spikes in the train. Because these interneurons typically fire bursts of up to five spikes during locomotor activity, this activity-dependent plasticity will presumably not contribute to the patterning of network activity. However, in the presence of the neuromodulators substance P and 5-HT, significant activity-dependent metaplasticity of these inputs developed over the first five spikes in the train. Substance P induced significant activity-dependent depression of inhibitory but potentiation of excitatory interneuron inputs, whereas 5-HT induced significant activity-dependent potentiation of both inhibitory and excitatory interneuron inputs. Because these metaplastic effects are consistent with the substance P and 5-HT-induced modulation of the network output, activity-dependent metaplasticity could be a potential mechanism underlying the coordination and modulation of rhythmic network activity. (+info)
Neural changes after operant conditioning of the aerial respiratory behavior in Lymnaea stagnalis.
In this study, we demonstrate neural changes that occurred during operant conditioning of the aerial respiratory behavior of Lymnaea stagnalis. Aerial respiration in Lymnaea occurs at the water interface and is achieved by opening and closing movements of its respiratory orifice, the pneumostome. This behavior is controlled by a central pattern generator (CPG), the neurons of which, as well as the motoneurons innervating the pneumostome, have previously been identified and their synaptic connections well characterized. The respiratory behavior was operantly conditioned by applying a mechanical stimulus to the open pneumostome whenever the animal attempted to breathe. This negative reinforcement to the open pneumostome resulted in its immediate closure and a significant reduction in the overall respiratory activity. Electrophysiological recordings from the isolated CNSs after operant conditioning showed that the spontaneous patterned respiratory activity of the CPG neurons was significantly reduced. This included reduced spontaneous activity of the CPG interneuron involved in pneumostome opening (input 3 interneuron) and a reduced frequency of spontaneous tonic activity of the CPG interneuron [right pedal dorsal 1 (RPeD1)]. The ability to trigger the patterned respiratory activity by electrical stimulation of RPeD1 was also significantly reduced after operant conditioning. This study therefore demonstrates significant changes within a CPG that are associated with changes in a rhythmic homeostatic behavior after operant conditioning. (+info)
GABAergic excitatory synapses and electrical coupling sustain prolonged discharges in the prey capture neural network of Clione limacina.
Afterdischarges represent a prominent characteristic of the neural network that controls prey capture reactions in the carnivorous mollusc Clione limacina. Their main functional implication is transformation of a brief sensory input from a prey into a lasting prey capture response. The present study, which focuses on the neuronal mechanisms of afterdischarges, demonstrates that a single pair of interneurons [cerebral A interneuron (Cr-Aint)] is responsible for afterdischarge generation in the network. Cr-Aint neurons are electrically coupled to all other neurons in the network and produce slow excitatory synaptic inputs to them. This excitatory transmission is found to be GABAergic, which is demonstrated by the use of GABA antagonists, uptake inhibitors, and double-labeling experiments showing that Cr-Aint neurons are GABA-immunoreactive. The Cr-Aint neurons organize three different pathways in the prey capture network, which provide positive feedback necessary for sustaining prolonged spike activity. The first pathway includes electrical coupling and slow chemical transmission from the Cr-Aint neurons to all other neurons in the network. The second feedback is based on excitatory reciprocal connections between contralateral interneurons. Recurrent excitation via the contralateral cell can sustain prolonged interneuron firing, which then drives the activity of all other cells in the network. The third positive feedback is represented by prominent afterdepolarizing potentials after individual spikes in the Cr-Aint neurons. Afterdepolarizations apparently represent recurrent GABAergic excitatory inputs. It is suggested here that these afterdepolarizing potentials are produced by GABAergic excitatory autapses. (+info)
even-skipped determines the dorsal growth of motor axons in Drosophila.
Axon pathfinding and target choice are governed by cell type-specific responses to external cues. Here, we show that in the Drosophila embryo, motorneurons with targets in the dorsal muscle field express the homeobox gene even-skipped and that this expression is necessary and sufficient to direct motor axons into the dorsal muscle field. Previously, it was shown that motorneurons projecting to ventral targets express the LIM homeobox gene islet, which is sufficient to direct axons to the ventral muscle field. Thus, even-skipped complements the function of islet, and together these two genes constitute a bimodal switch regulating axonal growth and directing motor axons to ventral or to dorsal regions of the muscle field. (+info)
Multiple point electrical stimulation of ulnar and median nerves.
A computer-assisted method of isolating single motor units (MUs) by multiple point stimulation (MPS) of peripheral nerves is described. MPS was used to isolate 10-30 single MUs from thenar and hypothenar muscles of normal subjects and patients with entrapment neuropathies, with the original purpose of obtaining a more representative mean motor unit potential for estimating the number of MUs in a muscle. The two important results that evolved from MPS however, were: (1) in the absence of 'alternation' MUs were recruited in an orderly pattern from small to large, and from longer to shorter latencies by graded electrical stimulation in both normal and pathological cases, (2) a comparison of the sizes of MUs recruited by stimulation proximal and distal to the elbow suggested that axonal branching can occur in the forearm 200 mm or more proximal to the motor point in intrinsic hand muscles. (+info)
Role of mitochondrial dysfunction in the Ca2+-induced decline of transmitter release at K+-depolarized motor neuron terminals.
The present study tested whether a Ca2+-induced disruption of mitochondrial function was responsible for the decline in miniature endplate current (MEPC) frequency that occurs with nerve-muscle preparations maintained in a 35 mM potassium propionate (35 mM KP) solution containing elevated calcium. When the 35 mM KP contained control Ca2+ (1 mM), the MEPC frequency increased and remained elevated for many hours, and the mitochondria within twitch motor neuron terminals were similar in appearance to those in unstimulated terminals. All nerve terminals accumulated FM1-43 when the dye was present for the final 6 min of a 300-min exposure to 35 mM KP with control Ca2+. In contrast, when Ca2+ was increased to 3.6 mM in the 35 mM KP solution, the MEPC frequency initially reached frequencies >350 s-1 but then gradually fell approaching frequencies <50 s-1. A progressive swelling and eventual distortion of mitochondria within the twitch motor neuron terminals occurred during prolonged exposure to 35 mM KP with elevated Ca2+. After approximately 300 min in 35 mM KP with elevated Ca2+, only 58% of the twitch terminals accumulated FM1-43. The decline in MEPC frequency in 35 mM KP with elevated Ca2+ was less when 15 mM glucose was present or when preparations were pretreated with 10 microM oligomycin and then bathed in the 35 mM KP with glucose. When glucose was present, with or without oligomycin pretreatment, a greater percentage of twitch terminals accumulated FM1-43. However, the mitochondria in these preparations were still greatly swollen and distorted. We propose that prolonged depolarization of twitch motor neuron terminals by 35 mM KP with elevated Ca2+ produced a Ca2+-induced decrease in mitochondrial ATP production. Under these conditions, the cytosolic ATP/ADP ratio was decreased thereby compromising both transmitter release and refilling of recycled synaptic vesicles. The addition of glucose stimulated glycolysis which contributed to the maintenance of required ATP levels. (+info)
Actions of a pair of identified cerebral-buccal interneurons (CBI-8/9) in Aplysia that contain the peptide myomodulin.
A combination of biocytin back-fills of the cerebral-buccal connectives and immunocytochemistry of the cerebral ganglion demonstrated that of the 13 bilateral pairs of cerebral-buccal interneurons in the cerebral ganglion, a subpopulation of 3 are immunopositive for the peptide myomodulin. The present paper describes the properties of two of these cells, which we have termed CBI-8 and CBI-9. CBI-8 and CBI-9 were found to be dye coupled and electrically coupled. The cells have virtually identical properties, and consequently we consider them to be "twin" pairs and refer to them as CBI-8/9. CBI-8/9 were identified by electrophysiological criteria and then labeled with dye. Labeled cells were found to be immunopositive for myomodulin, and, using high pressure liquid chromatography, the cells were shown to contain authentic myomodulin. CBI-8/9 were found to receive synaptic input after mechanical stimulation of the tentacles. They also received excitatory input from C-PR, a neuron involved in neck lengthening, and received a slow inhibitory input from CC5, a cell involved in neck shortening, suggesting that CBI-8/9 may be active during forward movements of the head or buccal mass. Firing of CBI-8 or CBI-9 resulted in the activation of a relatively small number of buccal neurons as evidenced by extracellular recordings from buccal nerves. Firing also produced local movements of the buccal mass, in particular a strong contraction of the I7 muscle, which mediates radula opening. CBI-8/9 were found to produce a slow depolarization and rhythmic activity of B48, the motor neuron for the I7 muscle. The data provide continuing evidence that the small population of cerebral buccal interneurons is composed of neurons that are highly diverse in their functional roles. CBI-8/9 may function as a type of premotor neuron, or perhaps as a peptidergic modulatory neuron, the functions of which are dependent on the coactivity of other neurons. (+info)