Synaptic drive in spinal motoneurons during scratch network activity.

Synaptic activity in motoneurons may provide unique insight in the relation between functional network activity and behavior. During scratch network activity in an ex vivo preparation from red-eared turtles ( Trachemys scripta elegans), excitatory and inhibitory synaptic current can be separated and quantified in voltage-clamp recordings. With this technique, we confirm the reciprocal synaptic excitation and inhibition in hip flexor motoneurons during ipsilateral scratching and show that out-of-phase inhibition and excitation also characterize hip extensor motoneurons during ipsi- and contralateral scratching.

Synaptic Excitation in Spinal Motoneurons Alternates with Synaptic Inhibition and Is Balanced by Outward Rectification during Rhythmic Motor Network Activity.

Regular firing in spinal motoneurons of red-eared turtles (, either sex) evoked by steady depolarization at rest is replaced by irregular firing during functional network activity. The transition caused by increased input conductance and synaptic fluctuations in membrane potential was suggested to originate from intense concurrent inhibition and excitation. We show that the conductance increase in motoneurons during functional network activity is mainly caused by intrinsic outward rectification near threshold for action potentials by activation of voltage and Ca gated K channels.

Motor Neurons.

Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional properties of this facility in the path from synaptic sites to the motor axon is reviewed with emphasis on voltage sensitive ion channels and regulatory metabotropic transmitter pathways.

Irregular Firing and High-Conductance States in Spinal Motoneurons during Scratching and Swimming.

Unlabelled: Intense synaptic transmission during scratch network activity increases conductance and induces irregular firing in spinal motoneurons. It is not known whether this high-conductance state is a select feature for scratching or a property that goes with spinal motor network activity in general. Here we compare conductance and firing patterns in spinal motoneurons during network activity for scratching and swimming in an ex vivo carapace-spinal cord preparation from adult turtles (Trachemys scripta elegans).

Dense distributed processing in a hindlimb scratch motor network.

In reduced preparations, hindlimb movements can be generated by a minimal network of neurons in the limb innervating spinal segments. The network of neurons that generates real movements is less well delineated. In an ex vivo carapace-spinal cord preparation from adult turtles (Trachemys scripta elegans), we show that ventral horn interneurons in mid-thoracic spinal segments are functionally integrated in the hindlimb scratch network.

Excitatory and inhibitory synaptic mechanisms at the first stage of integration in the electroreception system of the shark.

High impulse rate in afferent nerves is a common feature in many sensory systems that serve to accommodate a wide dynamic range. However, the first stage of integration should be endowed with specific properties that enable efficient handling of the incoming information. In elasmobranches, the afferent nerve originating from the ampullae of Lorenzini targets specific neurons located at the Dorsal Octavolateral Nucleus (DON), the first stage of integration in the electroreception system.

Increased activity of pre-motor network does not change the excitability of motoneurons during protracted scratch initiation.

Intrinsic response properties of neurons change during network activity. These changes may reinforce the initiation of particular forms of network activity. If so, the involvement of neurons in particular behaviours in multifunctional networks could be determined by up- or down-regulation of their intrinsic excitability.

Mathematical model of dopamine autoreceptors and uptake inhibitors and their influence on tonic and phasic dopamine signaling.

Dopamine (DA) D2-like autoreceptors are an important component of the DA system, but their influence on postsynaptic DA signaling is not well understood. They are, directly or indirectly, involved in drug abuse and in treatment of schizophrenia and attention deficit hyperactive disorder: DA autoreceptors influence the behavioral effect of cocaine and methylphenidate and may be the target of antipsychotic medications such as haloperidol. DA autoreceptors are active at two levels: Somatodendritic autoreceptors mainly influence firing rate of DA neurons, and presynaptic autoreceptors control release of neurotransmitter at axonal terminals.

Opposing Effects of Intrinsic Conductance and Correlated Synaptic Input on V-Fluctuations during Network Activity.

Neurons often receive massive concurrent bombardment of synaptic inhibition and excitation during functional network activity. This increases membrane conductance and causes fluctuations in membrane potential (V(m)) and spike timing. The conductance increase is commonly attributed to synaptic conductance, but also includes the intrinsic conductances recruited during network activity.

Inhibition of motoneurons during the cutaneous silent period in the spinal cord of the turtle.

The transient suppression of motor activity in the spinal cord after a cutaneous stimulus is termed the cutaneous silent period (CSP). It is not known if CSP is due to suppression of the premotor network or direct inhibition of motoneurons. This issue was examined by intracellular recordings from motoneurons in the isolated carapace-spinal cord preparation from adult turtles during rhythmic scratch-like reflex.

Voltage fluctuations in neurons: signal or noise?

Noise and variability are fundamental companions to ion channels and synapses and thus inescapable elements of brain function. The overriding unresolved issue is to what extent noise distorts and limits signaling on one hand and at the same time constitutes a crucial and fundamental enrichment that allows and facilitates complex adaptive behavior in an unpredictable world. Here we review the growing experimental evidence that functional network activity is associated with intense fluctuations in membrane potential and spike timing.

Motoneuron membrane potentials follow a time inhomogeneous jump diffusion process.

Stochastic leaky integrate-and-fire models are popular due to their simplicity and statistical tractability. They have been widely applied to gain understanding of the underlying mechanisms for spike timing in neurons, and have served as building blocks for more elaborate models. Especially the Ornstein-Uhlenbeck process is popular to describe the stochastic fluctuations in the membrane potential of a neuron, but also other models like the square-root model or models with a non-linear drift are sometimes applied.

Stereological estimate of the total number of neurons in spinal segment D9 of the red-eared turtle.

The red-eared turtle is an important animal model for investigating the neural activity in the spinal circuit that generates motor behavior. However, basic anatomical features, including the number of neurons in the spinal segments involved, are unknown. In the present study, we estimate the total number of neurons in segment D9 of the spinal cord in the red-eared turtle (Trachemys scripta elegans) using stereological cell counting methods.

Influence of phasic and tonic dopamine release on receptor activation.

Tonic and phasic dopamine release is implicated in learning, motivation, and motor functions. However, the relationship between spike patterns in dopaminergic neurons, the extracellular concentration of dopamine, and activation of dopamine receptors remains unresolved. In the present study, we develop a computational model of dopamine signaling that give insight into the relationship between the dynamics of release and occupancy of D(1) and D(2) receptors.

Signaling in large-scale neural networks.

We examine the recent finding that neurons in spinal motor circuits enter a high conductance state during functional network activity. The underlying concomitant increase in random inhibitory and excitatory synaptic activity leads to stochastic signal processing. The possible advantages of this metabolically costly organization are analyzed by comparing with synaptically less intense networks driven by the intrinsic response properties of the network neurons.

Organization of projection-specific interneurons in the spinal cord of the red-eared turtle.

Using differential retrograde axonal tracing, we identified motoneurons (MNs) and projection-specific interneuron (IN) classes in lumbar segment D9 of the adult red-eared turtle spinal cord. We characterized the distribution of these neurons in the transverse plane, and estimated their numbers and proportions. Different labeling paradigms allowed us to distinguish ipsilateral INs (IINs) from commissural INs (CINs), and to identify IINs and CINs with either ascending (a) axons, descending (d) axons, or axons that bifurcate to both ascend and descend (ad).

Intense synaptic activity enhances temporal resolution in spinal motoneurons.

In neurons, spike timing is determined by integration of synaptic potentials in delicate concert with intrinsic properties. Although the integration time is functionally crucial, it remains elusive during network activity. While mechanisms of rapid processing are well documented in sensory systems, agility in motor systems has received little attention.

Balanced inhibition and excitation drive spike activity in spinal half-centers.

Many limb movements are composed of alternating flexions and extensions. However, the underlying spinal network mechanisms remain poorly defined. Here, we show that the intensity of synaptic excitation and inhibition in limb motoneurons varies in phase rather than out of phase during rhythmic scratchlike network activity in the turtle.

Heterosynaptic modulation of the dorsal root potential in the turtle spinal cord in vitro.

In the somatosensory system, the flow of sensory information is regulated at early stages by presynaptic inhibition. Recent findings have shown that the mechanisms generating the primary afferent depolarization (PAD) associated with presynaptic inhibition are complex, with some components mediated by a non-spiking mechanism. How sensory inputs carried by neighbouring afferent fibres interact to regulate the generation of PAD, and thus presynaptic inhibition, is poorly known.

Conditional intrinsic voltage oscillations in mature vertebrate neurons undergo specific changes in culture.

Although intrinsic neuronal properties in invertebrates are well known to undergo specific adaptive changes in culture, long-term adaptation of similar properties in mature vertebrate neurons remain poorly understood. To investigate this, we used an organotypic slice preparation from the spinal cord of adult turtles maintainable for several weeks in culture conditions. N-methyl-D-aspartate (NMDA)-induced-tetrodotoxin (TTX)-resistant voltage oscillations in motoneurons were approximately 10 times faster in culture than in acute preparations.

Cellular signalling properties in microcircuits.

Molecules and cells are the signalling elements in microcircuits. Recent studies have uncovered bewildering diversity in postsynaptic signalling properties in all areas of the vertebrate nervous system. Major effort is now being invested in establishing the specialized signalling properties at the cellular and molecular levels in microcircuits in specific brain regions.

Influence of membrane properties on spike synchronization in neurons: theory and experiments.

In the brain spike synchronization in neurons is involved in information transfer and certain forms of dysfunction. The theory of random point processes was used to relate the statistical properties of input point processes to synchronization between firing in neurons viewed as threshold devices. Derived analytical relations describe normalized synchronization in the case of shared input with balanced excitation and inhibition.

Metabotropic modulation of motoneurons by scratch-like spinal network activity.

Glutamate is the main excitatory transmitter in the spinal motor network. The excitation is to a large extent mediated by ionotropic receptors, but glutamate also activates metabotropic receptors. In motoneurons in spinal cord slices the activation of group I metabotropic glutamate (mGlu1) receptors leads to facilitation of CaV1.

Subcellular distribution of L-type Ca2+ channels responsible for plateau potentials in motoneurons from the lumbar spinal cord of the turtle.

L-type calcium channels mediate the persistent inward current underlying plateau potentials in spinal motoneurons. Electrophysiological analysis shows that plateau potentials are generated by a persistent inward current mediated by low threshold L-type calcium channels located in the dendrites. As motoneurons express L-type calcium channels of the CaV1.