Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism.
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MAG is a potent inhibitor of axonal regeneration. Here, inhibition by MAG, and myelin in general, is blocked if neurons are exposed to neurotrophins before encountering the inhibitor; priming cerebellar neurons with BDNF or GDNF, but not NGF, or priming DRG neurons with any of these neurotrophins blocks inhibition by MAG/myelin. Dibutyryl cAMP also overcomes inhibition by MAG/myelin, and cAMP is elevated by neurotrophins. A PKA inhibitor present during priming abrogates the block of inhibition. Finally, if neurons are exposed to MAG/myelin and neurotrophins simultaneously, but with the Gi protein inhibitor, inhibition is blocked. We suggest that priming neurons with particular neurotrophins elevates cAMP and activates PKA, which blocks subsequent inhibition of regeneration and that priming is required because MAG/myelin activates a Gi protein, which blocks increases in cAMP. This is important for encouraging axons to regrow in vivo. (+info)
Receptor mechanisms underlying heterogenic reflexes among the triceps surae muscles of the cat.
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The soleus (S), medial gastrocnemius (MG), and lateral gastrocnemius (LG) muscles of the cat are interlinked by rapid spinal reflex pathways. In the decerebrate state, these heterogenic reflexes are either excitatory and length dependent or inhibitory and force dependent. Mechanographic analysis was used to obtain additional evidence that the muscle spindle primary ending and the Golgi tendon organ provide the major contributions to these reflexes, respectively. The tendons of the triceps surae muscles were separated and connected to independent force transducers and servo-controlled torque motors in unanesthetized, decerebrate cats. The muscles were activated as a group using crossed-extension reflexes. Electrical stimulation of the caudal cutaneous sural nerve was used to provide a particularly strong activation of MG and decouple the forces of the triceps surae muscles. During either form of activation, the muscles were stretched either individually or in various combinations to determine the strength and characteristics of autogenic and heterogenic feedback. The corresponding force responses, including both active and passive components, were measured during the changing background tension. During activation of the entire group, the excitatory, heterogenic feedback linking the three muscles was found to be strongest onto LG and weakest onto MG, in agreement with previous results concerning the strengths of heteronymous Ia excitatory postsynaptic potentials among the triceps surae muscles. The inhibition, which is known to affect only the soleus muscle, was dependent on active contractile force and was detected essentially as rapidly as length dependent excitation. The inhibition outlasted the excitation and was blocked by intravenous strychnine. These results indicate that the excitatory and inhibitory effects are dominated by feedback from primary spindle receptors and Golgi tendon organs. The interactions between these two feedback pathways potentially can influence both the mechanical coupling between ankle and knee. (+info)
C-PR neuron of Aplysia has differential effects on "Feeding" cerebral interneurons, including myomodulin-positive CBI-12.
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Head lifting and other aspects of the appetitive central motive state that precedes consummatory feeding movements in Aplysia is promoted by excitation of the C-PR neuron. Food stimuli activate C-PR as well as a small population of cerebral-buccal interneurons (CBIs). We wished to determine if firing of C-PR produced differential effects on the various CBIs or perhaps affected all the CBIs uniformly as might be expected for a neuron involved in producing a broad undifferentiated arousal state. We found that when C-PR was fired, it produced a wide variety of effects on various CBIs. Firing of C-PR evoked excitatory input to a newly identified CBI (CBI-12) the soma of which is located in the M cluster near the previously identified CBI-2. CBI-12 shares certain properties with CBI-2, including a similar morphology and a capacity to drive rhythmic activity of the buccal-ganglion. Unlike CBI-2, CBI-12 exhibits myomodulin immunoreactivity. Furthermore when C-PR is fired, CBI-12 receives a polysynaptic voltage-dependent slow excitation, whereas, CBI-2 receives relatively little input. C-PR also polysynaptically excites other CBIs including CBI-1 and CBI-8/9 but produces inhibition in CBI-3. In addition, firing of C-PR inhibits plateau potentials in CBI-5/6. The data suggest that activity of C-PR may promote the activity of one subset of cerebral-buccal interneurons, perhaps those involved in ingestive behaviors that occur during the head-up posture. C-PR also inhibits some cerebral-buccal interneurons that may be involved in behaviors in which C-PR activity is not required or may even interfere with other feeding behaviors such as rejection or grazing, that occur with the head down. (+info)
Gating of afferent input by a central pattern generator.
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Intracellular recordings from the sole proprioceptor (the oval organ) in the crab ventilatory system show that the nonspiking afferent fibers from this organ receive a cyclic hyperpolarizing inhibition in phase with the ventilatory motor pattern. Although depolarizing and hyperpolarizing current pulses injected into a single afferent will reset the ventilatory motor pattern, the inhibitory input is of sufficient magnitude to block afferent input to the ventilatory central pattern generator (CPG) for approximately 50% of the cycle period. It is proposed that this inhibitory input serves to gate sensory input to the ventilatory CPG to provide an unambiguous input to the ventilatory CPG. (+info)
Phase-dependent presynaptic modulation of mechanosensory signals in the locust flight system.
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In the locust flight system, afferents of a wing hinge mechanoreceptor, the hindwing tegula, make monosynaptic excitatory connections with motoneurons of the elevator muscles. During flight motor activity, the excitatory postsynaptic potentials (EPSPs) produced by these connections changed in amplitude with the phase of the wingbeat cycle. The largest changes occurred around the phase where elevator motoneurons passed through their minimum membrane potential. This phase-dependent modulation was neither due to flight-related oscillations in motoneuron membrane potential nor to changes in motoneuron input resistance. This indicates that modulation of EPSP amplitude is mediated by presynaptic mechanisms that affect the efficacy of afferent synaptic input. Primary afferent depolarizations (PADs) were recorded in the terminal arborizations of tegula afferents, presynaptic to elevator motoneurons in the same hemiganglion. PADs were attributed to presynaptic inhibitory input because they reduced the input resistance of the afferents and were sensitive to the gamma-aminobutyric acid antagonist picrotoxin. PADs occurred either spontaneously or were elicited by spike activity in the tegula afferents. In summary, afferent signaling in the locust flight system appears to be under presynaptic control, a candidate mechanism of which is presynaptic inhibition. (+info)
Temperature-dependent modulation of excitatory transmission in hippocampal slices is mediated by extracellular adenosine.
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Although extracellular adenosine concentrations in brain are increased markedly by a variety of stimuli such as hypoxia and ischemia, it has been difficult to demonstrate large increases in adenosine with stimuli that do not result in pathological tissue damage. The present studies demonstrate that increasing the temperature at which rat hippocampal brain slices are maintained (typically from 32.5 to 38.5 degrees C) markedly inhibits excitatory synaptic transmission. This effect was reversible on cooling, readily repeatable, and was blocked by A1 receptor antagonists and by adenosine deaminase, suggesting that it was mediated by increased activation of presynaptic adenosine A1 receptors by endogenous adenosine. This increase in adenosinergic inhibition was not a response to hyperthermia per se, because it could be elicited by temperatures that remained entirely within the hypothermic range (e. g., from 32.5 to 35.5 degrees C). The increased activity at A1 receptors appeared to be attributable to the direct release of adenosine via nucleoside transporters; the release of adenine nucleotides, linked to either the activation of NMDA receptors or the increased efflux of cAMP, appeared not to be involved. These results suggest that changes in brain temperature can alter the regulation of extracellular adenosine in rat brain slices and that increased adenosine release may be an important regulatory mechanism for countering increased excitability consequent to increased brain temperature. (+info)
Coding of sound envelopes by inhibitory rebound in neurons of the superior olivary complex in the unanesthetized rabbit.
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Most natural sounds (e.g., speech) are complex and have amplitude envelopes that fluctuate rapidly. A number of studies have examined the neural coding of envelopes, but little attention has been paid to the superior olivary complex (SOC), a constellation of nuclei that receive information from the cochlear nucleus. We studied two classes of predominantly monaural neurons: those that displayed a sustained response to tone bursts and those that gave only a response to the tone offset. Our results demonstrate that the off neurons in the SOC can encode the pattern of amplitude-modulated sounds with high synchrony that is superior to sustained neurons. The upper cutoff frequency and highest modulation frequency at which significant synchrony was present were, on average, slightly higher for off neurons compared with sustained neurons. Finally, most sustained and off neurons encoded the level of pure tones over a wider range of intensities than those reported for auditory nerve fibers and cochlear nucleus neurons. A traditional view of inhibition is that it attenuates or terminates neural activity. Although this holds true for off neurons, the robust discharge when inhibition is released adds a new dimension. For simple sounds (i.e., pure tones), the off response can code a wide range of sound levels. For complex sounds, the off response becomes entrained to each modulation, resulting in a precise temporal coding of the envelope. (+info)
The superior olivary nucleus and its influence on nucleus laminaris: a source of inhibitory feedback for coincidence detection in the avian auditory brainstem.
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Located in the ventrolateral region of the avian brainstem, the superior olivary nucleus (SON) receives inputs from nucleus angularis (NA) and nucleus laminaris (NL) and projects back to NA, NL, and nucleus magnocellularis (NM). The reciprocal connections between the SON and NL are of particular interest because they constitute a feedback circuit for coincidence detection. In the present study, the chick SON was investigated. In vivo tracing studies show that the SON projects predominantly to the ipsilateral NM, NL, and NA. In vitro whole-cell recording reveals single-cell morphology, firing properties, and postsynaptic responses. SON neurons are morphologically and physiologically suited for temporal integration; their firing patterns do not reflect the temporal structure of their excitatory inputs. Of most interest, direct stimulation of the SON evokes long-lasting inhibition in NL neurons. The inhibition blocks both intrinsic spike generation and orthodromically evoked activity in NL neurons and can be eliminated by bicuculline methiodide, a potent antagonist for GABAA receptor-mediated neurotransmission. These results strongly suggest that the SON provides GABAergic inhibitory feedback to laminaris neurons. We discuss a mechanism whereby SON-evoked GABAergic inhibition can influence the coding of interaural time differences for sound localization in the avian auditory brainstem. (+info)