RESUMEN
A fundamental task of the visual system is to respond to both increases and decreases of luminance with action potentials (ON and OFF responses1-4). OFF responses are stronger, faster, and more salient than ON responses in primary visual cortex (V1) of both cats5,6 and primates,7,8 but in ferrets9 and mice,10 ON responses can be stronger, weaker,11 or balanced12 in comparison to OFF responses. These discrepancies could arise from differences in species, experimental techniques, or stimulus properties, particularly retinotopic location in the visual field, as has been speculated;9 however, the role of retinotopy for ON/OFF dominance has not been systematically tested across multiple scales of neural activity within species. Here, we measured OFF versus ON responses across large portions of visual space with silicon probe and whole-cell patch-clamp recordings in mouse V1 and lateral geniculate nucleus (LGN). We found that OFF responses dominated in the central visual field, whereas ON and OFF responses were more balanced in the periphery. These findings were consistent across local field potential (LFP), spikes, and subthreshold membrane potential in V1, and were aligned with spatial biases in ON and OFF responses in LGN. Our findings reveal that retinotopy may provide a common organizing principle for spatial modulation of OFF versus ON processing in mammalian visual systems.
Asunto(s)
Corteza Visual , Vías Visuales , Animales , Hurones , Cuerpos Geniculados/fisiología , Ratones , Estimulación Luminosa/métodos , Corteza Visual/fisiología , Vías Visuales/fisiologíaRESUMEN
The activity of basal ganglia input receiving motor thalamus (BGMT) makes a critical impact on motor cortical processing, but modification in BGMT processing with Parkinsonian conditions has not be investigated at the cellular level. Such changes may well be expected because of homeostatic regulation of neural excitability in the presence of altered synaptic drive with dopamine depletion. We addressed this question by comparing BGMT properties in brain slice recordings between control and unilaterally 6-hydroxydopamine hydrochloride (6-OHDA)-treated adult mice. At a minimum of one month after 6-OHDA treatment, BGMT neurons showed a highly significant increase in intrinsic excitability, which was primarily because of a decrease in M-type potassium current. BGMT neurons after 6-OHDA treatment also showed an increase in T-type calcium rebound spikes following hyperpolarizing current steps. Biophysical computer modeling of a thalamic neuron demonstrated that an increase in rebound spiking can also be accounted for by a decrease in the M-type potassium current. Modeling also showed that an increase in sag with hyperpolarizing steps found after 6-OHDA treatment could in part but not fully be accounted for by the decrease in M-type current. These findings support the hypothesis that homeostatic changes in BGMT neural properties following 6-OHDA treatment likely influence the signal processing taking place in the BG thalamocortical network in Parkinson's disease.
Asunto(s)
Trastornos Parkinsonianos , Tálamo , Animales , Ganglios Basales , Dopamina , Ratones , Oxidopamina/toxicidad , Trastornos Parkinsonianos/inducido químicamenteRESUMEN
BACKGROUND: Clinical studies implicate the perioperative period in cognitive complications, and increasing experimental evidence shows that the anesthetic agents can affect neuronal processes that underpin learning and memory. Calcineurin, a Ca-dependent phosphatase critically involved in synaptic plasticity, is activated after isoflurane exposure, but its role in the neurological response to anesthesia is unclear. METHODS: We investigated the effect of chronic calcineurin inhibition on postanesthetic cognitive function. Mice were treated with 30 minutes of isoflurane anesthesia during a chronic cyclosporine A regimen. Behavioral end points during the perianesthesia period were quantified. Visuospatial learning was assessed with the water radial arm maze. Total and biotinylated surface protein expression of the α5ß3γ2 γ-aminobutyric acid (GABA) type A receptors was measured. Expression of the GABA synthesis enzyme glutamate decarboxylase (GAD)-67 was also measured. RESULTS: Mice treated with cyclosporine A before anesthesia showed significant deficits in visuospatial learning compared to sham and cyclosporine A-treated mice (n = 10 per group, P = .0152, Tukey post hoc test). Induction and emergence were unaltered by cyclosporine A. Analysis of hippocampal protein expression revealed an increased surface expression of the α5 GABA type A receptor subunit after isoflurane treatment (P = .019, Dunnett post hoc testing), as well as a decrease in GAD-67 expression. Cyclosporine A did not rescue either effect. CONCLUSIONS: Our results confirm the work of others that isoflurane induces changes to inhibitory network function and exclude calcineurin inhibition via cyclosporine A as an intervention. Further, our studies suggest that calcineurin mediates a protective role in the neurological response to anesthesia, and patients receiving cyclosporine A may be an at-risk group for memory problems related to anesthesia.
Asunto(s)
Anestésicos por Inhalación/toxicidad , Conducta Animal/efectos de los fármacos , Inhibidores de la Calcineurina/toxicidad , Ciclosporina/toxicidad , Hipocampo/efectos de los fármacos , Isoflurano/toxicidad , Memoria/efectos de los fármacos , Conducta Espacial/efectos de los fármacos , Percepción Visual/efectos de los fármacos , Animales , Cognición/efectos de los fármacos , Glutamato Descarboxilasa/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiopatología , Masculino , Ratones Endogámicos C57BL , Receptores de GABA-A/metabolismo , Factores de TiempoRESUMEN
Hippocampal neuron plasticity is strongly associated with learning, memory, and cognition. In addition to modification of synaptic function and connectivity, the capacity of hippocampal neurons to undergo plasticity involves the ability to change nonsynaptic excitability. This includes altering the probability that EPSPs will generate action potentials (E-S plasticity). Epilepsy is a prevalent neurological disorder commonly associated with neuronal hyperexcitability and cognitive dysfunction. We examined E-S plasticity in chronically epileptic Sprague-Dawley rats 3-10 weeks after pilocarpine-induced status epilepticus CA1 neurons in hippocampal slices were assayed by whole-cell current clamp to measure EPSPs evoked by Schaffer collateral stimulation. Using a weak spike-timing-dependent protocol to induce plasticity, we found robust E-S potentiation in conjunction with weak long-term potentiation (LTP) in saline-treated rats. In pilocarpine-treated rats, a similar degree of LTP was found, but E-S potentiation was reduced. Additionally, the degree of E-S potentiation was not correlated with the degree of LTP for either group, suggesting that they independently contribute to neuronal plasticity. E-S potentiation also differed from LTP in that E-S plasticity could be induced solely from action potentials generated by postsynaptic current injection. The calcium chelating agent BAPTA in the intracellular solution blocked LTP and E-S potentiation, revealing the calcium dependence of both processes. These findings suggest that LTP and E-S potentiation have overlapping but nonidentical mechanisms of inducing neuronal plasticity that may independently contribute to cognitive disruptions observed in the chronic epileptic state.
Asunto(s)
Epilepsia del Lóbulo Temporal/fisiopatología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Hipocampo/efectos de los fármacos , Pilocarpina/farmacología , Estado Epiléptico/fisiopatología , Potenciales de Acción/efectos de los fármacos , Animales , Estimulación Eléctrica/métodos , Epilepsia del Lóbulo Temporal/inducido químicamente , Epilepsia del Lóbulo Temporal/patología , Potenciales Postsinápticos Excitadores/fisiología , Hipocampo/patología , Hipocampo/fisiopatología , Potenciación a Largo Plazo/efectos de los fármacos , Potenciación a Largo Plazo/fisiología , Agonistas Muscarínicos/farmacología , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Ratas Sprague-Dawley , Estado Epiléptico/inducido químicamente , Estado Epiléptico/patologíaRESUMEN
Anesthetics produce unconsciousness by modulating ion channels that control neuronal excitability. Research has shown that specific GABAA receptor (GABAAR) subtypes in particular regions of the central nervous system contribute to different hyperpolarizing conductances, and behaviorally to distinct components of the anesthetized state. The expression of these receptors on the neuron cell surface, and thus the strength of inhibitory neurotransmission, is dynamically regulated by intracellular trafficking mechanisms. Pharmacologic or activity-based perturbations to these regulatory systems have been implicated in pathology of several neurological conditions, and can alter the individual response to anesthesia. Furthermore, studies are beginning to uncover how anesthetic exposure itself elicits enduring changes in subcellular physiology, including the processes that regulate ion channel trafficking. Here, we review the mechanisms that determine GABAAR surface expression, and elaborate on influences germane to anesthesia and emergence. We address known trafficking differences between the intrasynaptic receptors that mediate phasic current and the extra-synaptic receptors mediating tonic current. We also describe neurophysiologic consequences and network-level abnormalities in brain function that result from receptor trafficking aberrations. We hypothesize that the relationship between commonly used anesthetic agents and GABAAR surface expression has direct consequences on mature functioning neural networks and by extension ultimately influence the outcome of patients that undergo general anesthesia. Rational design of new anesthetics, anesthetic techniques, EEG-based monitoring strategies, or emergence treatments will need to take these effects into consideration.
RESUMEN
Although antiretroviral (ARV) therapy has reduced the incidence of severe dementia associated with HIV infection, there has been a rise in milder neurocognitive complaints. Data from HIV patients taking ARVs have shown measurable neurocognitive improvements during drug cessation, suggesting a neurotoxic role of the therapy itself. Mechanisms underlying potential ARV neurotoxicity have not been thoroughly investigated, however pathologic oxidative stress and mitochondrial dysfunction have been suspected. Using DIV 16 primary rat cortical neuron culture, we tested eight ARVs from the three most commonly prescribed ARV classes: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) for effects on neuron viability and morphology after 24 h of drug exposure. Of the tested NRTIs, only stavudine at nearly 100 times the target plasma concentration affected neuron viability with no appreciable change in morphology. Dideoxyinosine induced dendritic simplification at 100 times target plasma concentrations, but did not adversely affect viability. The sole NtRTI, tenofovir, induced dendritic simplification at approximately 3-4 times target plasma concentration, but did not affect viability. Of the tested PIs, only amprenavir decreased neuron viability at nearly 100 times the target plasma concentration. The non-nucleoside reverse transcriptase inhibitor, efavirenz, consistently reduced viability (at 50 µM) and induced dendritic simplification (at 20 µM) nearest the target plasma concentration. Probing mitochondrial energetics of DIV16 cortical neurons after exposure to 20 µM efavirenz showed rapid diminution of mitochondrial-dependent oxygen consumption. Further, 20 µM efavirenz decreased excitability in ex vivo slice culture whereas 2 µM had no effect.
Asunto(s)
Fármacos Anti-VIH/toxicidad , Antirretrovirales/toxicidad , Benzoxazinas/toxicidad , Inhibidores de la Transcriptasa Inversa/toxicidad , Alquinos , Animales , Animales Recién Nacidos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/patología , Ciclopropanos , Relación Dosis-Respuesta a Droga , Masculino , Neuronas/efectos de los fármacos , Neuronas/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Antibiotics are used in the treatment and prevention of bacterial infections, but effects on neuron excitability have been documented. A recent study demonstrated that clarithromycin alleviates daytime sleepiness in hypersomnia patients (Trotti LM, Saini P, Freeman AA, Bliwise DL, García PS, Jenkins A, Rye DB. J Psychopharmacol 28: 697-702, 2014). To explore the potential application of clarithromycin as a stimulant, we performed whole cell patch-clamp recordings in rat pyramidal cells from the CA3 region of hippocampus. In the presence of the antibiotic, rheobase current was reduced by 50%, F-I relationship (number of action potentials as a function of injected current) was shifted to the left, and the resting membrane potential was more depolarized. Clarithromycin-induced hyperexcitability was dose dependent; doses of 30 and 300 µM clarithromycin significantly increased the firing frequency and membrane potential compared with controls (P = 0.003, P < 0.0001). We hypothesized that clarithromycin enhanced excitability by reducing GABAA receptor activation. Clarithromycin at 30 µM significantly reduced (P = 0.001) the amplitude of spontaneous miniature inhibitory GABAergic currents and at 300 µM had a minor effect on action potential width. Additionally, we tested the effect of clarithromycin in an ex vivo seizure model by evaluating its effect on spontaneous local field potentials. Bath application of 300 µM clarithromycin enhanced burst frequency twofold compared with controls (P = 0.0006). Taken together, these results suggest that blocking GABAergic signaling with clarithromycin increases cellular excitability and potentially serves as a stimulant, facilitating emergence from anesthesia or normalizing vigilance in hypersomnia and narcolepsy. However, the administration of clarithromycin should be carefully considered in patients with seizure disorders. NEW & NOTEWORTHY: Clinical administration of the macrolide antibiotic clarithromycin has been associated with side effects such as mania, agitation, and delirium. Here, we investigated the adverse effects of this antibiotic on CA3 pyramidal cell excitability. Clarithromycin induces hyperexcitability in single neurons and is related to a reduction in GABAergic signaling. Our results support a potentially new application of clarithromycin as a stimulant to facilitate emergence from anesthesia or to normalize vigilance.
Asunto(s)
Potenciales de Acción/efectos de los fármacos , Región CA3 Hipocampal/citología , Claritromicina/farmacología , Inhibidores de la Síntesis de la Proteína/farmacología , Células Piramidales/efectos de los fármacos , Receptores de GABA/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Animales Recién Nacidos , Biofisica , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Femenino , Técnicas In Vitro , Potenciales Postsinápticos Inhibidores/efectos de los fármacos , Masculino , Neurotransmisores/farmacología , Técnicas de Placa-Clamp , Células Piramidales/fisiología , Ratas , Ratas Sprague-DawleyRESUMEN
The active zone (AZ) is a thickening of the presynaptic membrane where exocytosis takes place. Chemical synapses contain neurotransmitter-loaded synaptic vesicles (SVs) that at rest are tethered away from the synaptic release site, but after the presynaptic inflow of Ca(+2) elicited by an action potential translocate to the AZ to release their neurotransmitter load. We report that tissue-type plasminogen activator (tPA) is stored outside the AZ of cerebral cortical neurons, either intermixed with small clear-core vesicles or in direct contact with the presynaptic membrane. We found that cerebral ischemia-induced release of neuronal tPA, or treatment with recombinant tPA, recruits the cytoskeletal protein ßII-spectrin to the AZ and promotes the binding of SVs to ßII-spectrin, enlarging the population of SVs in proximity to the synaptic release site. This effect does not require the generation of plasmin and is followed by the recruitment of voltage gated calcium channels (VGCC) to the presynaptic terminal that leads to Ca(+2)-dependent synapsin I phosphorylation, freeing SVs to translocate to the AZ to deliver their neurotransmitter load. Our studies indicate that tPA activates the SV cycle and induces the structural and functional changes in the synapse that are required for successful neurotransmission.
Asunto(s)
Corteza Cerebral/citología , Corteza Cerebral/efectos de los fármacos , Neuronas/efectos de los fármacos , Vesículas Sinápticas/efectos de los fármacos , Activador de Tejido Plasminógeno/farmacología , Potenciales de Acción/efectos de los fármacos , Animales , Isquemia Encefálica/patología , Canales de Calcio/efectos de los fármacos , Células Cultivadas , Exocitosis/efectos de los fármacos , Fibrinolisina/biosíntesis , Inmunohistoquímica , Masculino , Fosforilación/efectos de los fármacos , Terminales Presinápticos/efectos de los fármacos , Proteómica , Ratas , Ratas Sprague-Dawley , Espectrina/biosíntesis , Sinapsinas/metabolismoRESUMEN
This study examined whether activity is a contributing factor to motor terminal degeneration in mice that overexpress the G93A mutation of the SOD1 enzyme found in humans with inherited motor neuron disease. Previously, we showed that overload of muscles accomplished by synergist denervation accelerated motor terminal degeneration in dogs with hereditary canine spinal muscular atrophy (HCSMA). In the present study, we found that SOD1 plantaris muscles overloaded for 2months showed no differences of neuromuscular junction innervation status when compared with normally loaded, contralateral plantaris muscles. Complete elimination of motor terminal activity using blockade of sciatic nerve conduction with tetrodotoxin cuffs for 1month also produced no change of plantaris innervation status. To assess possible effects of activity on motor terminal function, we examined the synaptic properties of SOD1 soleus neuromuscular junctions at a time when significant denervation of close synergists had occurred as a result of natural disease progression. When examined in glucose media, SOD1 soleus synaptic properties were similar to wildtype. When glycolysis was inhibited and ATP production limited to mitochondria, however, blocking of evoked synaptic transmission occurred and a large increase in the frequency of spontaneous mEPCs was observed. Similar effects were observed at neuromuscular junctions in muscle from dogs with inherited motor neuron disease (HCSMA), although significant defects of synaptic transmission exist at these neuromuscular junctions when examined in glucose media, as reported previously. These results suggest that glycolysis compensates for mitochondrial dysfunction at motor terminals of SOD1 mice and HCSMA dogs. This compensatory mechanism may help to support resting and activity-related metabolism in the presence of dysfunctional mitochondria and prolong the survival of SOD1 motor terminals.
Asunto(s)
Glucólisis/fisiología , Enfermedad de la Neurona Motora/fisiopatología , Neuronas Motoras/patología , Unión Neuromuscular/patología , Superóxido Dismutasa/genética , Animales , Perros , Ratones , Ratones Transgénicos , Enfermedad de la Neurona Motora/genética , Enfermedad de la Neurona Motora/metabolismo , Enfermedad de la Neurona Motora/patología , Neuronas Motoras/metabolismo , Músculo Esquelético/inervación , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatología , Unión Neuromuscular/metabolismo , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1RESUMEN
BACKGROUND: Motor neuron degeneration in SOD1(G93A) transgenic mice begins at the nerve terminal. Here we examine whether this degeneration depends on expression of mutant SOD1 in muscle fibers. METHODOLOGY/PRINCIPAL FINDINGS: Hindlimb muscles were transplanted between wild-type and SOD1(G93A) transgenic mice and the innervation status of neuromuscular junctions (NMJs) was examined after 2 months. The results showed that muscles from SOD1(G93A) mice did not induce motor terminal degeneration in wildtype mice and that muscles from wildtype mice did not prevent degeneration in SOD1(G93A) transgenic mice. Control studies demonstrated that muscles transplanted from SOD1(G93A) mice continued to express mutant SOD1 protein. Experiments on wildtype mice established that the host supplied terminal Schwann cells (TSCs) at the NMJs of transplanted muscles. CONCLUSIONS/SIGNIFICANCE: These results indicate that expression of the mutant protein in muscle is not needed to cause motor terminal degeneration in SOD1(G93A) transgenic mice and that a combination of motor terminals, motor axons and Schwann cells, all of which express mutant protein may be sufficient.
Asunto(s)
Músculos/patología , Enfermedades Neurodegenerativas/genética , Superóxido Dismutasa/genética , Superóxido Dismutasa/fisiología , Animales , Femenino , Genotipo , Proteínas Fluorescentes Verdes/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Unión Neuromuscular/patología , Células de Schwann/citología , Superóxido Dismutasa-1RESUMEN
Peripheral nerve crush initiates a robust increase in transmission strength at spinal synapses made by axotomized group IA primary sensory neurons. To study the injury signal that initiates synaptic enhancement in vivo, we designed experiments to manipulate the enlargement of EPSPs produced in spinal motoneurons (MNs) by IA afferents 3 d after nerve crush in anesthetized adult rats. If nerve crush initiates IA EPSP enlargement as proposed by reducing impulse-evoked transmission in crushed IA afferents, then restoring synaptic activity should eliminate enlargement. Daily electrical stimulation of the nerve proximal to the crush site did, in fact, eliminate enlargement but was, surprisingly, just as effective when the action potentials evoked in crushed afferents were prevented from propagating into the spinal cord. Consistent with its independence from altered synaptic activity, we found that IA EPSP enlargement was also eliminated by colchicine blockade of axon transport in the crushed nerve. Together with the observation that colchicine treatment of intact nerves had no short-term effect on IA EPSPs, we conclude that enhancement of IA-MN transmission is initiated by some yet to be identified positive injury signal generated independent of altered synaptic activity. The results establish a new set of criteria that constrain candidate signaling molecules in vivo to ones that develop quickly at the peripheral injury site, move centrally by axon transport, and initiate enhanced transmission at the central synapses of crushed primary sensory afferents through a mechanism that can be modulated by action potential activity restricted to the axons of crushed afferents.
Asunto(s)
Neuronas Motoras/fisiología , Sinapsis/fisiología , Transmisión Sináptica/fisiología , Nervio Tibial/lesiones , Nervio Tibial/fisiología , Animales , Potenciales Postsinápticos Excitadores/fisiología , Femenino , Compresión Nerviosa , Ratas , Ratas WistarRESUMEN
Available evidence supports the idea that muscle fibres provide retrograde signals that enable the expression of adult motoneuron electrical properties but the mechanisms remain unknown. We showed recently that when acetylcholine receptors are blocked at motor endplates, the electrical properties of rat motoneurons change in a way that resembles changes observed after axotomy. This observation suggests that receptor blockade and axotomy interrupt the same signalling mechanisms but leaves open the possibility that the loss of muscle fibre activity underlies the observed effects. To address this issue, we examined the electrical properties of axotomized motoneurons following reinnervation. Ordinarily, these properties return to normal following reinnervation and re-activation of muscle, but in this study muscle fibre activity and evoked acetylcholine release were prevented during reinnervation by blocking axonal conduction. Under these conditions, the properties of motoneurons that successfully reinnervated muscle fibres recovered to normal despite the absence of muscle fibre activity and evoked release. We conclude that the expression of motoneuron electrical properties is not regulated by muscle fibre activity but rather by a retrograde signalling system coupled to activation of endplate acetylcholine receptors. Our results indicate that spontaneous release of acetylcholine from regenerated motor terminals is sufficient to operate the system.
Asunto(s)
Acetilcolina/metabolismo , Neuronas Motoras/fisiología , Músculo Esquelético/inervación , Animales , Electromiografía , Potenciales Evocados/fisiología , Femenino , Placa Motora/fisiología , Ratas , Ratas Wistar , Receptores Colinérgicos/fisiología , Transducción de Señal/fisiología , Transmisión Sináptica/fisiologíaRESUMEN
Long after a cut peripheral nerve reinnervates muscle and restores force production in adult cats, the muscle does not respond reflexively to stretch. Motivated by the likelihood that stretch areflexia is related to problems with sensing and controlling limb position after peripheral neuropathies, we sought to determine the underlying mechanism. Electrophysiological and morphological measurements were made in anesthetized rats having one of the nerves to the triceps surae muscles either untreated or cut and immediately rejoined surgically many months earlier. First, it was established that reinnervated muscles failed to generate stretch reflexes, extending observations of areflexia to a second species. Next, multiple elements in the sensorimotor circuit of the stretch reflex were examined in both the PNS and CNS. Encoding of muscle stretch by regenerated proprioceptive afferents was remarkably similar to normal, although we observed some expected abnormalities, e.g., increased length threshold. However, the robust stretch-evoked sensory response that arrived concurrently at the CNS in multiple proprioceptive afferents produced synaptic responses that were either smaller than normal or undetectable. Muscle stretch failed to evoke detectable synaptic responses in 13 of 22 motoneurons, although electrical stimulation generated monosynaptic excitatory postsynaptic potentials that were indistinguishable from normal. The ineffectiveness of muscle stretch was not attributable therefore to dysfunction at synapses made between regenerated Ia afferents and motoneurons. Among multiple candidate mechanisms, we suggest that centrally controlled neural circuits may actively suppress the sensory information encoded by regenerated proprioceptive afferents to prevent recovery of the stretch reflex.
Asunto(s)
Vías Aferentes/fisiología , Neuronas Motoras/fisiología , Músculo Esquelético/fisiología , Regeneración Nerviosa/fisiología , Inhibición Neural/fisiología , Propiocepción/fisiología , Animales , Electromiografía/métodos , Potenciales Postsinápticos Excitadores/fisiología , Potenciales Postsinápticos Excitadores/efectos de la radiación , Femenino , Lateralidad Funcional , Inmunohistoquímica/métodos , Husos Musculares/fisiología , Músculo Esquelético/citología , Estimulación Física/métodos , Ratas , Ratas Wistar , Recuperación de la Función/fisiología , Reflejo de Estiramiento/fisiología , Ubiquitina Tiolesterasa/metabolismoRESUMEN
Among the mechanisms that may result in modulation of the stretch reflex by the recent history of muscle contraction is the history dependence observed under some conditions in the response properties of muscle spindles. The present study was designed to test one report that in successive trials of muscle stretch-release, spindle afferent firing during stretch, i.e., the dynamic response shows no history dependence beyond the initial burst of firing at stretch onset. Firing responses of spindle afferents were recorded during sets of three consecutive trials of triangular stretch-release applied to triceps surae muscles in barbiturate-anesthetized rats. All 69 spindle afferents fired more action potentials (spikes) during the dynamic response of the first trial, excluding the initial burst, than in the following two trials. The reduced dynamic response (RDR) was nearly complete after trial 1 and amounted to an average of approximately 12 fewer spikes (16 pps slower firing rate) in trial 3 than in trial 1. RDR was sensitive to the interval between stretch sets but independent of stretch velocity (4-32 mm/s). RDR was reflected in the synaptic potentials recorded intracellularly from 16 triceps surae alpha-motoneurons: depolarization during muscle stretch was appreciably reduced after trial 1. These findings demonstrate history dependence of spindle afferent responses that extends throughout the dynamic response in successive muscle stretches and that is synaptically transmitted to motoneurons with the probable effect, unless otherwise compensated, of modulating the stretch reflex.