RESUMEN
We conducted a quantitative analysis of the different nonspiking interneurons in the local pattern-generating circuits of the crayfish swimmeret system. Within each local circuit, these interneurons control the firing of the power-stroke and return-stroke motor neurons that drive swimmeret movements. Fifty-four of these interneurons were identified during physiological experiments with sharp microelectrodes and filled with dextran Texas red, Neurobiotin, or both. Five types of neurons were identified on the basis of combinations of physiological and anatomical characteristics. Anatomical categories were based on 16 anatomical parameters measured from stacks of confocal images obtained from each neuron. The results support the recognition of two functional classes: inhibitors of power stroke (IPS) and inhibitors of return stroke (IRS). The IPS class of interneuron has three morphological types with similar physiological properties. The IRS class has two morphological types with physiological properties and anatomical features different from the IPS neurons but similar within the class. Three of these five types have not been previously identified. Reviewing the evidence for dye coupling within each type, we conclude that each type of IPS neuron and one type of IRS neuron occur as a single copy in each local pattern-generating circuit. The last IRS type includes neurons that might occur as a dye-coupled pair in each local circuit. Recognition of these different interneurons in the swimmeret pattern-generating circuits leads to a refined model of the local pattern-generating circuit that includes synaptic connections that encode and decode information required for intersegmental coordination of swimmeret movements.
Asunto(s)
Generadores de Patrones Centrales/fisiología , Interneuronas/clasificación , Interneuronas/fisiología , Animales , Astacoidea , Técnicas In Vitro , Interneuronas/citologíaRESUMEN
Experimental and corresponding modeling studies indicate that there is a 2- to 5-fold variation of intrinsic and synaptic parameters across animals while functional output is maintained. Here, we review experiments, using the heartbeat central pattern generator (CPG) in medicinal leeches, which explore the consequences of animal-to-animal variation in synaptic strength for coordinated motor output. We focus on a set of segmental heart motor neurons that all receive inhibitory synaptic input from the same four premotor interneurons. These four premotor inputs fire in a phase progression and the motor neurons also fire in a phase progression because of differences in synaptic strength profiles of the four inputs among segments. Our work tested the hypothesis that functional output is maintained in the face of animal-to-animal variation in the absolute strength of connections because relative strengths of the four inputs onto particular motor neurons is maintained across animals. Our experiments showed that relative strength is not strictly maintained across animals even as functional output is maintained, and animal-to-animal variations in strength of particular inputs do not correlate strongly with output phase. Further experiments measured the precise temporal pattern of the premotor inputs, the segmental synaptic strength profiles of their connections onto motor neurons, and the temporal pattern (phase progression) of those motor neurons all in the same animal for a series of 12 animals. The analysis of input and output in this sample of 12 individuals suggests that the number (four) of inputs to each motor neuron and the variability of the temporal pattern of input from the CPG across individuals weaken the influence of the strength of individual inputs. Moreover, the temporal pattern of the output varies as much across individuals as that of the input. Essentially, each animal arrives at a unique solution for how the network produces functional output.
Asunto(s)
Hirudo medicinalis/fisiología , Neuronas Motoras/fisiología , Red Nerviosa/fisiología , Animales , Estimulación Eléctrica , Ganglios de Invertebrados/fisiología , Corazón/fisiología , Frecuencia Cardíaca/fisiología , Interneuronas/fisiología , Inhibición Neural , Especificidad de la Especie , Sinapsis/fisiología , Transmisión SinápticaRESUMEN
Previously, we reported a canonical ensemble model of the heart motoneurons that underlie heartbeat in the medicinal leech. The model motoneurons contained a minimal set of electrical intrinsic properties and received a synaptic input pattern based on measurements performed in the living system. Although the model captured the synchronous and peristaltic motor patterns observed in the living system, it did not match quantitatively the motor output observed. Because the model motoneurons had minimal intrinsic electrical properties, the mismatch between model and living system suggests a role for additional intrinsic properties in generating the motor pattern. We used the dynamic clamp to test this hypothesis. We introduced the same segmental input pattern used in the model to motoneurons isolated pharmacologically from their endogenous input in the living system. We show that, although the segmental input pattern determines the segmental phasing differences observed in motoneurons, the intrinsic properties of the motoneurons play an important role in determining their phasing, particularly when receiving the synchronous input pattern. We then used trapezoidal input waveforms to show that the intrinsic properties present in the living system promote phase advances compared with our model motoneurons. Electrical coupling between heart motoneurons also plays a role in shaping motoneuron output by synchronizing the activity of the motoneurons within a segment. These experiments provide a direct assessment of how motoneuron intrinsic properties interact with their premotor pattern of synaptic drive to produce rhythmic output.
Asunto(s)
Potenciales de Acción/fisiología , Corazón/fisiología , Neuronas Motoras/fisiología , Animales , Corazón/inervación , Interneuronas/fisiología , Sanguijuelas , Sinapsis/fisiologíaRESUMEN
Previously we presented a quantitative description of the spatiotemporal pattern of inhibitory synaptic input from the heartbeat central pattern generator (CPG) to segmental motor neurons that drive heartbeat in the medicinal leech and the resultant coordination of CPG interneurons and motor neurons. To begin elucidating the mechanisms of coordination, we explore intersegmental and side-to-side coordination in an ensemble model of all heart motor neurons and their known synaptic inputs and electrical coupling. Model motor neuron intrinsic properties were kept simple, enabling us to determine the extent to which input and electrical coupling acting together can account for observed coordination in the living system in the absence of a substantive contribution from the motor neurons themselves. The living system produces an asymmetric motor pattern: motor neurons on one side fire nearly in synchrony (synchronous), whereas on the other they fire in a rear-to-front progression (peristaltic). The model reproduces the general trends of intersegmental and side-to-side phase relations among motor neurons, but the match with the living system is not quantitatively accurate. Thus realistic (experimentally determined) inputs do not produce similarly realistic output in our model, suggesting that motor neuron intrinsic properties may contribute to their coordination. By varying parameters that determine electrical coupling, conduction delays, intraburst synaptic plasticity, and motor neuron excitability, we show that the most important determinant of intersegmental and side-to-side phase relations in the model was the spatiotemporal pattern of synaptic inputs, although phasing was influenced significantly by electrical coupling.
Asunto(s)
Sinapsis Eléctricas/fisiología , Sistema de Conducción Cardíaco/fisiología , Frecuencia Cardíaca/fisiología , Sanguijuelas/fisiología , Modelos Biológicos , Neuronas Motoras/fisiología , Potenciales de Acción/fisiología , Animales , Relación Dosis-Respuesta en la Radiación , Estimulación Eléctrica/métodos , Interneuronas/fisiología , Potenciales de la Membrana/fisiología , Potenciales de la Membrana/efectos de la radiación , Inhibición Neural/fisiologíaRESUMEN
Two cardinal features of Parkinson's disease (PD) pathophysiology are a loss of glutamatergic synapses paradoxically accompanied by an increased glutamatergic transmission to the striatum. The exact substrate of this increased glutamatergic drive remains unclear. The striatum receives glutamatergic inputs from the thalamus and the cerebral cortex. Using vesicular glutamate transporters (vGluTs) 1 and 2 as markers of the corticostriatal and thalamostriatal afferents, respectively, we examined changes in the synaptology and relative prevalence of striatal glutamatergic inputs in methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys using electron microscopic immunoperoxidase and confocal immunofluorescence methods. Our findings demonstrate that the prevalence of vGluT1-containing terminals is significantly increased in the striatum of MPTP-treated monkeys (51.9 +/- 3.5% to 66.5 +/- 3.4% total glutamatergic boutons), without any significant change in the pattern of synaptic connectivity; more than 95% of vGluT1-immunolabeled terminals formed axo-spinous synapses in both conditions. In contrast, the prevalence of vGluT2-immunoreactive terminals did not change after MPTP treatment (21.7 +/- 1.3% vs. 21.6 +/- 1.2% total glutamatergic boutons). However, a substantial increase in the ratio of axo-spinous to axo-dendritic synapses formed by vGluT2-immunoreactive terminals was found in the pre-caudate and post-putamen striatal regions of MPTP-treated monkeys, suggesting a certain degree of synaptic reorganization of the thalamostriatal system in parkinsonism. About 20% of putative glutamatergic terminals did not show immunoreactivity in striatal tissue immunostained for both vGluT1 and vGluT2, suggesting the expression of another vGluT in these boutons. These findings provide striking evidence that suggests a differential degree of plasticity of the corticostriatal and thalamostriatal system in PD.
Asunto(s)
Corteza Cerebral/fisiología , Cuerpo Estriado/fisiología , Intoxicación por MPTP/fisiopatología , Plasticidad Neuronal/fisiología , Sinapsis/fisiología , Tálamo/fisiología , Animales , Corteza Cerebral/patología , Cuerpo Estriado/patología , Femenino , Intoxicación por MPTP/patología , Macaca mulatta , Vías Nerviosas/patología , Vías Nerviosas/fisiología , Ratas , Sinapsis/patología , Tálamo/patologíaRESUMEN
The striatum is divided into two compartments named the patch (or striosome) and the matrix. Although these two compartments can be differentiated by their neurochemical content or afferent and efferent projections, the synaptology of inputs to these striatal regions remains poorly characterized. By using the vesicular glutamate transporters vGluT1 and vGluT2, as markers of corticostriatal and thalamostriatal projections, respectively, we demonstrate a differential pattern of synaptic connections of these two pathways between the patch and the matrix compartments. We also demonstrate that the majority of vGluT2-immunolabeled axon terminals form axospinous synapses, suggesting that thalamic afferents, like corticostriatal inputs, terminate preferentially onto spines in the striatum. Within both compartments, more than 90% of vGluT1-containing terminals formed axospinous synapses, whereas 87% of vGluT2-positive terminals within the patch innervated dendritic spines, but only 55% did so in the matrix. To characterize further the source of thalamic inputs that could account for the increase in axodendritic synapses in the matrix, we undertook an electron microscopic analysis of the synaptology of thalamostriatal afferents to the matrix compartments from specific intralaminar, midline, relay, and associative thalamic nuclei in rats. Approximately 95% of PHA-L-labeled terminals from the central lateral, midline, mediodorsal, lateral dorsal, anteroventral, and ventral anterior/ventral lateral nuclei formed axospinous synapses, a pattern reminiscent of corticostriatal afferents but strikingly different from thalamostriatal projections arising from the parafascicular nucleus (PF), which terminated onto dendritic shafts. These findings provide the first evidence for a differential pattern of synaptic organization of thalamostriatal glutamatergic inputs to the patch and matrix compartments. Furthermore, they demonstrate that the PF is the sole source of significant axodendritic thalamic inputs to striatal projection neurons. These observations pave the way for understanding differential regulatory mechanisms of striatal outflow from the patch and matrix compartments by thalamostriatal afferents.
Asunto(s)
Vías Aferentes/fisiología , Cuerpo Estriado/metabolismo , Sinapsis/metabolismo , Tálamo/metabolismo , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo , Vías Aferentes/citología , Animales , Western Blotting/métodos , Cuerpo Estriado/anatomía & histología , Lateralidad Funcional , Inmunohistoquímica/métodos , Masculino , Microscopía Inmunoelectrónica/métodos , Modelos Anatómicos , Fitohemaglutininas/metabolismo , Ratas , Ratas Sprague-Dawley , Sinapsis/clasificación , Sinapsis/ultraestructura , Tálamo/anatomía & histología , Proteína 1 de Transporte Vesicular de Glutamato/metabolismoRESUMEN
This modeling study investigates the functional role of pacemaker neurons in generating stable rhythms in the pre-Botzinger complex, a subcircuit of the respiratory pattern-generating circuitry in mammals. While the presence of pacemakers within the network is without doubt, the percentage and significance of such pacemakers is still unresolved. Here we revisited earlier network simulations by varying the fraction of pacemaker and non-pacemaker neurons within the network, and quantifying the robustness of the input parameter space and range of frequencies output by the network. Stable network rhythms were possible even with no pacemakers. However, we found that a network of at least 50% pacemakers produced the greatest range of output frequencies and had the more robust input space.