RESUMO
Neurodegenerative diseases are among the main causes of death in the United States, leading to irreversible disintegration of neurons. Despite intense international research efforts, cellular mechanisms that initiate neurodegeneration remain elusive, thus inhibiting the development of effective preventative and early onset medical treatment. To identify underlying cellular mechanisms that initiate neuron degeneration, it is critical to identify histological and cellular hallmarks that can be linked to underlying biochemical processes. Due to the poor tissue preservation of degenerating mammalian brain tissue, our knowledge regarding histopathological hallmarks of early to late degenerative stages is only fragmentary. Here, we introduce a novel model organism to study histological hallmarks of neurodegeneration, the spider Cupiennius salei. We utilized toluidine blue-stained 0.9-µm serial semithin and 50-nm ultrathin sections of young and old spider nervous tissue. Our findings suggest that the initial stages of neurodegeneration in spiders may be triggered by (1) dissociation of neuron- and glia-derived microtubules, and (2) the weakening of microtubule-associated desmosomal junctions that lead to the unraveling of neuron-insulating macroglia, compromising the structural integrity of affected neurons. The involvement of macroglia in the disposal of neuronal debris described here-although different in the proposed transport mechanisms-shows resemblance to the mammalian glymphatic system. We propose that this model system is highly suitable to investigate invertebrate neurodegenerative processes from early onset to scar formation and that this knowledge may be useful for the study of neurodegeneration in mammalian tissue.
Assuntos
Neurônios , Aranhas , Animais , Adesão Celular , Neurônios/metabolismo , Encéfalo , Microtúbulos , Invertebrados , MamíferosRESUMO
Steroid sex hormones drive changes in the nervous system and behavior in many animal taxa, but integrating the former with the latter remains challenging. One useful model system for meeting this challenge is seasonally breeding songbirds. In these species, plasma testosterone levels rise and fall across the seasons, altering song behavior and causing dramatic growth and regression of the song-control system, a discrete set of nuclei that control song behavior. Whereas the cellular mechanisms underlying changes in nucleus volume have been studied as a model for neural growth and degeneration, it is unknown whether these changes in neural structure are accompanied by changes in electrophysiological properties other than spontaneous firing rate. Here we test the hypothesis that passive and active neuronal properties in the forebrain song-control nuclei HVC and RA change across breeding conditions. We exposed adult male Gambel's white-crowned sparrows to either short-day photoperiod or long-day photoperiod and systemic testosterone to simulate nonbreeding and breeding conditions, respectively. We made whole-cell recordings from RA and HVC neurons in acute brain slices. We found that RA projection neuron membrane time constant, capacitance, and evoked and spontaneous firing rates were all increased in the breeding condition; the measured electrophysiological properties of HVC interneurons and projection neurons were stable across breeding conditions. This combination of plastic and stable intrinsic properties could directly impact the song-control system's motor control across seasons, underlying changes in song stereotypy. These results provide a valuable framework for integrating how steroid hormones modulate cellular physiology to change behavior.
Assuntos
Androgênios/farmacologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Prosencéfalo/citologia , Pardais/fisiologia , Testosterona/farmacologia , Vocalização Animal/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Análise de Variância , Androgênios/sangue , Animais , Biofísica , Estimulação Elétrica , Masculino , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/classificação , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp/métodos , Fotoperíodo , Radioimunoensaio/métodos , Testosterona/sangue , Fatores de TempoRESUMO
The rhythmic pyloric network of the lobster stomatogastric system approximately maintains phase (that is, the burst durations and durations between the bursts of its neurons change proportionally) when network cycle period is altered by current injection into the network pacemaker (Hooper, 1997a,b). When isolated from the network and driven by rhythmic hyperpolarizing current pulses, the delay to firing after each pulse of at least one network neuron type [pyloric (PY)] varies in a phase-maintaining manner when cycle period is varied (Hooper, 1998). These variations require PY neurons to have intrinsic mechanisms that respond to changes in neuron activity on time scales at least as long as 2 s. Slowly activating and deactivating conductances could provide such a mechanism. We tested this possibility by building models containing various slow conductances. This work showed that such conductances could indeed support intrinsic phase maintenance, and we show here results for one such conductance, a slow potassium conductance. These conductances supported phase maintenance because their mean activation level changed, hence altering neuron postinhibition firing delay, when the rhythmic input to the neuron changed. Switching the sign of the dependence of slow-conductance activation and deactivation on membrane potential resulted in neuron delays switching to change in an anti-phase-maintaining manner. These data suggest that slow conductances or similar slow processes such as changes in intracellular Ca(2+) concentration could underlie phase maintenance in pyloric network neurons.
Assuntos
Canais de Potássio de Retificação Tardia/fisiologia , Neurônios/fisiologia , Periodicidade , Piloro/inervação , Piloro/fisiologia , Potenciais de Ação/fisiologia , Animais , Gânglios dos Invertebrados/fisiologia , Rede Nervosa/fisiologia , Palinuridae/fisiologia , Piloro/citologiaRESUMO
In several systems, including some well studied invertebrate "model" preparations, rapid, rhythmic inputs drive slow muscles. In this situation muscle contractions can summate temporally between motor neuron bursts, tonically contract, and low-pass filter broad-band input. We have investigated how the muscles innervated by each motor neuron type of the rapid, rhythmic (cycle period, approximately 1 sec) lobster pyloric network respond when driven by previously recorded in vitro pyloric network activity from intact stomatogastric nervous systems. Under these conditions the much slower gastric mill and cardiac sac networks of the stomatogastric nervous system are also active and modify pyloric activity. All of the muscles show pyloric timed phasic contractions that ride on a sustained tonic contraction; muscle activity can range from being almost completely phasic to almost completely tonic. The modifications of pyloric neuron activity induced by gastric mill (cycle period, approximately 10 sec) activity result in some pyloric muscles showing prominent, gastric mill-timed, changes in either phasic or tonic contraction amplitude. The strong modification of pyloric neuron activity induced by cardiac sac (cycle period, approximately 60 sec) activity alters the contractions of all pyloric muscles. These changes are sufficient that for some muscles, in some preparations, the primary muscle output is cardiac sac-timed. This is the first work to examine the motor responses of all pyloric muscle classes to spontaneous stomatogastric activity and shows that the pyloric motor pattern is a complex combination of the activities of three neural networks, although only one (the pyloric) innervates the muscles.
Assuntos
Neurônios Motores/fisiologia , Músculos/fisiologia , Rede Nervosa/fisiologia , Palinuridae/fisiologia , Piloro/fisiologia , Animais , Contração Muscular/fisiologia , Músculos/inervação , PeriodicidadeRESUMO
Pyloric muscles of the stomatogastric neuromuscular system of the lobster Panulirus interruptus produce highly deterministic (range, less than +/- 6% of mean amplitude) contractions in response to motor nerve stimulation with unchanging spike bursts containing physiological (5-10) spike numbers. Intracellular recordings of extrajunctional potentials (EJPs) evoked in these muscles by motor nerve stimulation revealed a large, apparently stochastic amplitude variation (range, +/- 36% of mean amplitude). These observations raised the question of how do electrical responses with a large amplitude variation give rise to deterministic muscle output? We show here that this question is likely resolved by (1) combinatorial averaging within individual muscle fibers of the multiple EJPs that occur in motor neuron bursts, and (2) averaging across muscle fibers whose electrical responses are uncorrelated. Synapses with high inherent variability are also present in vertebrate CNSs. Combinatorial averaging in multispike inputs would also reduce variation in postsynaptic response at these synapses. The data reported here provide further support that bursting presynaptic activity could make such synapses functionally deterministic as well.
Assuntos
Contração Muscular/fisiologia , Músculos/fisiologia , Potenciais de Ação/fisiologia , Animais , Estimulação Elétrica , Eletrofisiologia , Técnicas In Vitro , Contração Isotônica/fisiologia , Modelos Lineares , Potenciais da Membrana/fisiologia , Neurônios Motores/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Músculos/inervação , Nephropidae , Processos EstocásticosRESUMO
Elasmobranch fishes produce some of the largest oocytes known, exceeding 10 cm in diameter. Using various microscopy techniques we investigated the structural adaptations which facilitate the production of these large egg cells in three species of shark: the Atlantic sharpnose shark, Rhizoprionodon terraenovae, dusky smoothound, Mustelus canis and the little gulper shark, Centrophorus uyato. The ovarian follicle of elasmobranchs follows the typical vertebrate pattern, with one notable exception; the zona pellucida reaches extreme widths, over 70 µm, during early oogenesis. Contact between the follicle cells and the oocyte across the zona pellucida is necessary for oogenesis. We describe here a novel set of large, tube-like structures, which we named follicle cell processes that bridge this gap. The follicle cell processes are more robust than the microvilli associated with the follicle cells and the oocyte plasma membrane and much longer. During early oogenesis the follicle increases in size relatively quickly resulting in a wide zona pellucida. At this stage the follicle cell processes appear taut, uniform and radially oriented. As oogenesis continues the zona pellucida narrows and the follicle cell processes change their orientation, appearing to wrap around the oocyte. The presence of the contractile protein actin within the follicle cell processes and their change in orientation may well be an adaptation for maintaining the integrity of these large oocytes. The follicle cell processes also contain electron dense material, identical to material found within the follicle cells, suggesting a role in the transport of metabolites to the developing oocyte.
Assuntos
Folículo Ovariano/anatomia & histologia , Tubarões/anatomia & histologia , Animais , Feminino , Humanos , Oócitos/citologia , Oogênese , Folículo Ovariano/ultraestrutura , Óvulo/citologia , Zona Pelúcida/ultraestruturaRESUMO
How can flexible phasing be generated by a central pattern generator (CPG)? To address this question, we have extended an existing model of the leech heartbeat CPG's timing network to construct a model of the CPG core and explore how appropriate phasing is set up by parameter variation. Within the CPG, the phasing among premotor interneurons switches regularly between two well defined states - synchronous and peristaltic. To reproduce experimentally observed phasing, we varied the strength of inhibitory synaptic and excitatory electrical input from the timing network to follower premotor interneurons. Neither inhibitory nor electrical input alone was sufficient to produce proper phasing on both sides, but instead a balance was required. Our model suggests that the different phasing of the two sides arises because the inhibitory synapses and electrical coupling oppose one another on one side (peristaltic) and reinforce one another on the other (synchronous). Our search of parameter space defined by the strength of inhibitory synaptic and excitatory electrical input strength led to a CPG model that well approximates the experimentally observed phase relations. The strength values derived from this analysis constitute model predictions that we tested by measurements made in the living system. Further, variation of the intrinsic properties of follower interneurons showed that they too systematically influence phasing. We conclude that a combination of inhibitory synaptic and excitatory electrical input interacting with neuronal intrinsic properties can flexibly generate a variety of phase relations so that almost any phasing is possible.
RESUMO
The central pattern generator (CPG) for heartbeat in leeches consists of seven identified pairs of segmental heart interneurons and one unidentified pair. Four of the identified pairs and the unidentified pair of interneurons make inhibitory synaptic connections with segmental heart motor neurons. The CPG produces a side-to-side asymmetric pattern of intersegmental coordination among ipsilateral premotor interneurons corresponding to a similarly asymmetric fictive motor pattern in heart motor neurons, and asymmetric constriction pattern of the two tubular hearts: synchronous and peristaltic. Using extracellular techniques, we recorded, in 61 isolated nerve cords, the activity of motor neurons in conjunction with the phase reference premotor heart interneuron, HN(4), and another premotor interneuron that allowed us to assess the coordination mode. These data were then coupled with a previous description of the temporal pattern of premotor interneuron activity in the two coordination modes to synthesize a global phase diagram for the known elements of the CPG and the entire motor neuron ensemble. These average data reveal the stereotypical side-to-side asymmetric patterns of intersegmental coordination among the motor neurons and show how this pattern meshes with the activity pattern of premotor interneurons. Analysis of animal-to-animal variability in this coordination indicates that the intersegmental phase progression of motor neuron activity in the midbody in the peristaltic coordination mode is the most stereotypical feature of the fictive motor pattern. Bilateral recordings from motor neurons corroborate the main features of the asymmetric motor pattern.
Assuntos
Coração/fisiologia , Interneurônios/fisiologia , Sanguessugas/fisiologia , Neurônios Motores/fisiologia , Miocárdio/citologia , Sinapses/fisiologia , Potenciais de Ação/fisiologia , Animais , Gânglios dos Invertebrados/citologia , Modelos Neurológicos , Contração Miocárdica , Inibição Neural/fisiologiaRESUMO
The central pattern generator (CPG) for heartbeat in medicinal leeches consists of seven identified pairs of segmental heart interneurons and one unidentified pair. Four of the identified pairs and the unidentified pair of interneurons make inhibitory synaptic connections with segmental heart motor neurons. The CPG produces a side-to-side asymmetric pattern of intersegmental coordination among ipsilateral premotor interneurons corresponding to a similarly asymmetric fictive motor pattern in heart motor neurons, and asymmetric constriction pattern of the two tubular hearts, synchronous and peristaltic. Using extracellular recordings from premotor interneurons and voltage-clamp recordings of ipsilateral segmental motor neurons in 69 isolated nerve cords, we assessed the strength and dynamics of premotor inhibitory synaptic output onto the entire ensemble of heart motor neurons and the associated conduction delays in both coordination modes. We conclude that premotor interneurons establish a stereotypical pattern of intersegmental synaptic connectivity, strengths, and dynamics that is invariant across coordination modes, despite wide variations among preparations. These data coupled with a previous description of the temporal pattern of premotor interneuron activity and relative phasing of motor neuron activity in the two coordination modes enable a direct assessment of how premotor interneurons through their temporal pattern of activity and their spatial pattern of synaptic connectivity, strengths, and dynamics coordinate segmental motor neurons into a functional pattern of activity.
Assuntos
Coração/fisiologia , Sanguessugas/fisiologia , Neurônios Motores/fisiologia , Dinâmica não Linear , Sinapses/fisiologia , Potenciais de Ação/fisiologia , Análise de Variância , Animais , Lateralidade Funcional , Potenciais Pós-Sinápticos Inibidores/fisiologia , Contração Miocárdica/fisiologiaRESUMO
The central pattern generator for heartbeat in medicinal leeches constitutes seven identified pairs of segmental heart interneurons. Four identified pairs of heart interneurons make a staggered pattern of inhibitory synaptic connections with segmental heart motor neurons. Using extracellular recording from multiple interneurons in the network in 56 isolated nerve cords, we show that this pattern generator produces a side-to-side asymmetric pattern of intersegmental coordination among ipsilateral premotor interneurons. This pattern corresponds to a similarly asymmetric fictive motor pattern in heart motor neurons and asymmetric constriction pattern of the two tubular hearts, synchronous and peristaltic. We provide a quantitative description of the firing pattern of all the premotor interneurons, including phase, duty cycle, and intraburst frequency of this premotor activity pattern. This analysis identifies two stereotypical coordination modes corresponding to synchronous and peristaltic, which show phase constancy over a broad range of periods as do the fictive motor pattern and the heart constriction pattern. Coordination mode is controlled through one segmental pair of heart interneurons (switch interneurons). Side-to-side switches in coordination mode are a regular feature of this pattern generator and occur with changes in activity state of these switch interneurons. Associated with synchronous coordination of premotor interneurons, the ipsilateral switch interneuron is in an active state, during which it produces rhythmic bursts, whereas associated with peristaltic coordination, the ipsilateral switch interneuron is largely silent. We argue that timing and pattern elaboration are separate functions produced by overlapping subnetworks in the heartbeat central pattern generator.
Assuntos
Gânglios dos Invertebrados/fisiologia , Hirudo medicinalis/fisiologia , Potenciais de Ação/fisiologia , Animais , Coração/inervação , Coração/fisiologia , Frequência Cardíaca , Interneurônios/fisiologia , Neurônios Motores/fisiologia , Sinapses/fisiologiaRESUMO
Distributed neural networks (ones characterized by high levels of interconnectivity among network neurons) are not well understood. Increased insight into these systems can be obtained by perturbing network activity so as to study the functions of specific neurons not only in the network's "baseline" activity but across a range of network activities. We applied this technique to study cycle period control in the rhythmic pyloric network of the lobster, Panulirus interruptus. Pyloric rhythmicity is driven by an endogenous oscillator, the Anterior Burster (AB) neuron. Two network neurons feed back onto the pacemaker, the Lateral Pyloric (LP) neuron by inhibition and the Ventricular Dilator (VD) neuron by electrical coupling. LP and VD neuron effects on pyloric cycle period can be studied across a range of periods by altering period by injecting current into the AB neuron and functionally removing (by hyperpolarization) the LP and VD neurons from the network at each period. Within a range of pacemaker periods, the LP and VD neurons regulate period in complementary ways. LP neuron removal speeds the network and VD neuron removal slows it. Outside this range, network activity is disrupted because the LP neuron cannot follow slow periods, and the VD neuron cannot follow fast periods. These neurons thus also limit, in complementary ways, normal pyloric activity to a certain period range. These data show that follower neurons in pacemaker networks can play central roles in controlling pacemaker period and suggest that in some cases specific functions can be assigned to individual network neurons.
Assuntos
Relógios Biológicos/fisiologia , Neurônios/fisiologia , Palinuridae/fisiologia , Animais , Feminino , Gânglios dos Invertebrados/citologia , Gânglios dos Invertebrados/fisiologia , Masculino , Vias Neurais/fisiologia , Periodicidade , Piloro/inervaçãoRESUMO
The lobster pyloric network has a densely interconnected synaptic connectivity pattern, and the role individual synapses play in generating network activity is consequently difficult to discern. We examined this issue by quantifying the effect on pyloric network phasing and spiking activity of removing the Lateral Pyloric (LP) and Ventricular Dilator (VD) neurons, which synapse onto almost all pyloric neurons. A confounding factor in this work is that LP and VD neuron removal alters pyloric cycle period. To determine the effects of LP and VD neuron removal on pyloric activity independent of these period alterations, we altered network period by current injection into a pyloric pacemaker neuron, hyperpolarized the LP or VD neuron to functionally remove each from the network, and plotted various measures of pyloric neuron activity against period with and without the LP or VD neuron. In normal physiological saline, in many (or most) cases removing either neuron had surprisingly little effect on the activity of its postsynaptic partners, which suggests that under these conditions these neurons play a relatively small role in determining pyloric activity. In the cases in which removal did alter postsynaptic activity, the effects were inconsistent across preparations, which suggests that either despite producing very similar neural outputs, pyloric networks from different animals have different cellular and synaptic properties, or some synapses contribute to network activity only under certain modulatory conditions, and the "baseline" level of modulatory influence the network receives from higher centers varies from animal to animal.