Biomedical subjects

Paul S Katz

Publications and source records attributed to Paul S Katz.

13 recordsLinked to original sources

PubMed2007

Role of membrane potential in calcium signaling during rhythmic bursting in tritonia swim interneurons.

Rhythmic bursting in neurons is accompanied by dynamic changes in intracellular Ca(2+) concentration. These Ca(2+) signals may be caused by membrane potential changes during bursting and/or by synaptic inputs. We determined that membrane potential is responsible for most, if not all, of the cytoplasmic Ca(2+) signal recorded during rhythmic bursting in two neurons of the escape swim central pattern generator (CPG) of the mollusk, Tritonia diomedea: ventral swim interneuron B (VSI) and cerebral neuron 2 (C2). Ca(2+) signals were imaged with a confocal laser scanning microscope while the membrane potential was recorded at the soma. During the swim motor pattern (SMP), Ca(2+) signals in both neurons transiently increased during each burst of action potentials with a more rapid decay in secondary than in primary neurites. VSI and C2 were then voltage-clamped at the soma, and each neuron's own membrane potential waveform recorded during the SMP was played back as the voltage command. In all regions of VSI, this completely reproduced the amplitude and time course of Ca(2+) signals observed during the SMP, but in C2, the amplitude was lower in the playback experiments than during the SMP, possibly due to space clamp problems. Therefore in VSI, the cytoplasmic Ca(2+) signal during the SMP can be accounted for by its membrane potential excursions, whereas in C2 the membrane potential excursions can account for most of the SMP Ca(2+) signal.

Animals↗

PubMed2006

Homologues of serotonergic central pattern generator neurons in related nudibranch molluscs with divergent behaviors.

Homologues of a neuron that contributes to a species-specific behavior were identified and characterized in species lacking that behavior. The nudibranch Tritonia diomedea swims by flexing its body dorsally and ventrally. The dorsal swim interneurons (DSIs) are components of the central pattern generator (CPG) underlying this rhythmic motor pattern and also activate crawling. Homologues of the DSIs were identified in six nudibranchs that do not exhibit dorsal-ventral swimming: Tochuina tetraquetra, Melibe leonina, Dendronotus iris, D. frondosus, Armina californica, and Triopha catalinae. Homology was based upon shared features that distinguish the DSIs from all other neurons: (1) serotonin immunoreactivity, (2) location in the Cerebral serotonergic posterior (CeSP) cluster, and (3) axon projection to the contralateral pedal ganglion. The DSI homologues, named CeSP-A neurons, share additional features with the DSIs: irregular basal firing, synchronous inputs, electrical coupling, and reciprocal inhibition. Unlike the DSIs, the CeSP-A neurons were not rhythmically active in response to nerve stimulation. The CeSP-A neurons in Tochuina and Triopha also excited homologues of the Tritonia Pd5 neuron, a crawling efferent. Thus, the CeSP-A neurons and the DSIs may be part of a conserved network related to crawling that may have been co-opted into a rhythmic swim CPG in Tritonia.

Action Potentials↗

PubMed2006

Evolution and development of neural circuits in invertebrates.

Developmental mechanisms can shed light on how evolutionary diversity has arisen. Invertebrate nervous systems offer a wealth of diverse structures and functions from which to relate development to evolution. Individual homologous neurons have been shown to have distinct roles in species with different behaviors. In addition, specific neurons have been lost or gained in some phylogenetic lineages. The ability to address the neural basis of behavior at the cellular level in invertebrates has facilitated discoveries showing that species-specific behavior can arise from differences in synaptic strength, in neuronal structure and in neuromodulation. The mechanisms involved in the development of neural circuits lead to these differences across species.

Animals↗

PubMed2006

Comparative mapping of serotonin-immunoreactive neurons in the central nervous systems of nudibranch molluscs.

The serotonergic systems in nudibranch molluscs were compared by mapping the locations of serotonin-immunoreactive (5-HT-ir) neurons in 11 species representing all four suborders of the nudibranch clade: Dendronotoidea (Tritonia diomedea, Tochuina tetraquetra, Dendronotus iris, Dendronotus frondosus, and Melibe leonina), Aeolidoidea (Hermissenda crassicornis and Flabellina trophina), Arminoidea (Dirona albolineata, Janolus fuscus, and Armina californica), and Doridoidea (Triopha catalinae). A nomenclature is proposed to standardize reports of cell location in species with differing brain morphologies. Certain patterns of 5-HT immunoreactivity were found to be consistent for all species, such as the presence of 5-HT-ir neurons in the pedal and cerebral ganglia. Also, particular clusters of 5-HT-ir neurons in the anterior and posterior regions of the dorsal surface of the cerebral ganglion were always present. However, there were interspecies differences in the number of 5-HT-ir neurons in each cluster, and some clusters even exhibited strong intraspecies variability that was only weakly correlated with brain size. Phylogenetic analysis suggests that the presence of particular classes of 5-HT-ir neurons exhibits a great deal of homoplasy. The conserved features of the nudibranch serotonergic system presumably represent the shared ancestral structure, whereas the derived characters suggest substantial independent evolutionary changes in the number and presence of serotonergic neurons. Although a number of studies have demonstrated phylogenetic variability of peptidergic systems, this study suggests that serotonergic systems may also exhibit a high degree of homoplasy in some groups of organisms.

Animals↗

PubMed2006

Comparative neurophysiology: an electric convergence in fish.

Two lineages of fishes convergently evolved electric organs; recent research has shown that they independently took advantage of an extra copy of a sodium channel gene to alter channel kinetics for the electric organ discharge.

Amino Acid Sequence↗

PubMed2006

Serotonergic enhancement of a 4-AP-sensitive current mediates the synaptic depression phase of spike timing-dependent neuromodulation.

The mechanism underlying spike timing-dependent neuromodulation (STDN) was investigated in the opisthobranch mollusc Tritonia diomedea. The serotonergic dorsal swim interneurons (DSIs) dynamically modulated the synaptic output of ventral swim interneuron B (VSI); immediately after DSI stimulation, there was a potentiation of VSI synaptic strength followed by a longer-lasting synaptic depression. The potentiation phase of STDN was unaffected by spike broadening produced by the potassium channel blocker 4-aminopyridine (4-AP). In contrast, the depression phase was eliminated by 4-AP. Bath-applied serotonin (5-HT) decreased VSI spike duration and increased the magnitude of the A-current (IA), a voltage-dependent, transient, outward current. 4-AP preferentially blocked IA and prevented the spike narrowing caused by 5-HT, uncovering the full extent of 5-HT-induced synaptic potentiation. A consistent correlation was observed between IA and spike duration, but the correlation between synaptic strength and spike duration differed between preparations. Conductance-based simulations showed that the magnitude of A-current conductance could affect spike duration and gave an estimation of the change needed to produce spike narrowing. An artificial IA introduced into the VSI in the presence of 4-AP by means of the dynamic-clamp technique restored spike duration and gave a further approximation of the magnitude of modulation needed for spike narrowing. Together, these results suggest a mechanism for STDN: the DSIs release 5-HT, which causes a spike duration-independent enhancement of synaptic strength and a longer-lasting enhancement of IA that narrows the VSI spike and hence decreases VSI synaptic strength. Thus, STDN arises from the dynamics of independent intracellular signaling events.

4-Aminopyridine↗

PubMed2006

A distributed computing tool for generating neural simulation databases.

After developing a model neuron or network, it is important to systematically explore its behavior across a wide range of parameter values or experimental conditions, or both. However, compiling a very large set of simulation runs is challenging because it typically requires both access to and expertise with high-performance computing facilities. To lower the barrier for large-scale model analysis, we have developed NeuronPM, a client/server application that creates a "screen-saver" cluster for running simulations in NEURON (Hines & Carnevale, 1997). NeuronPM provides a user-friendly way to use existing computing resources to catalog the performance of a neural simulation across a wide range of parameter values and experimental conditions. The NeuronPM client is a Windows-based screen saver, and the NeuronPM server can be hosted on any Apache/PHP/MySQL server. During idle time, the client retrieves model files and work assignments from the server, invokes NEURON to run the simulation, and returns results to the server. Administrative panels make it simple to upload model files, define the parameters and conditions to vary, and then monitor client status and work progress. NeuronPM is open-source freeware and is available for download at http://neuronpm.homeip.net . It is a useful entry-level tool for systematically analyzing complex neuron and network simulations.

Animals↗

PubMed2005

Pharmacological manipulation of serotonin levels in the nervous system of the opisthobranch mollusc Tritonia diomedea.

Serotonin-related disorders can be treated by manipulating serotonin synthesis with the serotonin precursor 5-hydroxytryptophan (5-HTP) or other pharmacological agents. The mollusc Tritonia diomedea is a model for investigating the effects of altering serotonin content on the functions of identified neurons. We used high-performance liquid chromatography and immunohistochemistry to examine the amount and localization of 5-HTP, serotonin, and the serotonin breakdown product 5-hydroxyindolacetic acid (5-HIAA) in the Tritonia brain after various pharmacological treatments. Exposure to 5-HTP (2 mM for 30 min-1 h) caused an immediate and massive increase in total 5-HTP content, which lasted more than 20 h, and the widespread appearance of 5-HTP immunoreactivity in neurons. Serotonin levels rose gradually, but only a restricted number of additional neurons displayed serotonin immunoreactivity. 5-HTP treatment also caused an increase in the total amount of 5-HIAA and the appearance of 5-HIAA immunoreactivity throughout the brain. Treatment with the synthesis cofactor tetrahydrobiopterin, the initial precursor tryptophan, or serotonin itself had no persistent effect on total serotonin content. The amino acid decarboxylase inhibitor hydroxybenzylhydrazine (NSD-1015) also had no effect on the total serotonin content, although it caused an accumulation of 5-HTP. Thus, serotonin levels in the brain of T. diomedea appear to be maintained by a homeostatic mechanism that can be disrupted by 5-HTP.

5-Hydroxytryptophan↗

PubMed2004

Cycle period of a network oscillator is independent of membrane potential and spiking activity in individual central pattern generator neurons.

Rhythmic motor patterns are thought to arise through the cellular properties and synaptic interactions of neurons in central pattern generator (CPG) circuits. Yet, when examining the CPG underlying the rhythmic escape response of the opisthobranch mollusc, Tritonia diomedea, we found that the cycle period of the fictive swim motor pattern recorded from the isolated nervous system was not altered by changing the resting membrane potential or the level of spiking activity of any of the 3 known CPG cell types: ventral swim interneuron-B (VSI-B), the dorsal swim interneurons (DSIs), and cerebral neuron 2 (C2). Furthermore, tonic firing in one or more DSIs or C2 evoked rhythmic bursting that did not differ from the cycle period of the motor pattern evoked by nerve stimulation, regardless of the firing frequency. In contrast, the CPG produced a large range of cycle periods as a function of temperature. The temperature sensitivity of the fictive motor pattern produced by the isolated nervous system was similar to the temperature sensitivity of the swimming behavior produced by the intact animal. Thus, although the CPG is capable of producing a wide range of cycle periods under the influence of temperature, the membrane potentials and spiking activity of the identified CPG neurons do not determine the periodicity of the motor pattern. This suggests that the timing of activity in this network oscillator may be determined by a mechanism that is independent of the membrane potentials and spike rate of its constituent neurons.

Action Potentials↗

PubMed2004

The effect of oral 5-HTP administration on 5-HTP and 5-HT immunoreactivity in monoaminergic brain regions of rats.

5-Hydroxytryptophan (5-HTP), which is the rate-limiting precursor in serotonin (5-hydroxytryptamine (5-HT)) biosynthesis, is used as an oral supplement to enhance serotonin levels in humans. To evaluate its effects on serotonin levels and localization, 5-hydroxytryptophan was administered to Sprague-Dawley rats either orally or via intraperitoneal injection. 5-Hydroxytryptophan-immunoreactivity was co-localized with serotonin-immunoreactivity in the serotonergic dorsal raphe nucleus of control animals and this was not changed in animals given 5-hydroxytryptophan. Oral 5-HTP administration increased the intensity of both 5-HTP and serotonin immunoreactivity in raphe neurons. However, 5-HTP treatment also caused ectopic 5-hydroxytryptophan-immunoreactivity and serotonin-immunoreactivity in normally dopaminergic neurons of the substantia nigra par compacta. Serotonin-immunoreactivity was confined to neurons that also displayed amino acid decarboxylase immunoreactivity, but in a small percentage of substantia nigra neurons, serotonin immunoreactivity was not co-localized with tyrosine hydroxylase-immunoreactivity. The intensity of the immunoreactivity to serotonin and 5-hydroxytryptophan in the substantia nigra was maximal within 2h of 5-hydroxytryptophan administration and returned to control levels by 24h. This time course mirrored changes in HPLC measurements of 5-hydroxytryptophan, serotonin, and the metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the urine. 5-Hydroxytryptophan administration did not cause ectopic appearance of either serotonin or 5-hydroxytryptophan in the noradrenergic locus coeruleus. These results suggest that a single oral dose of 5-HTP increases the 5-HTP and serotonin content of serotonergic neurons and causes the transient ectopic appearance of serotonin in some normally non-serotonergic neurons.

5-Hydroxytryptophan↗

PubMed2003

Spike timing-dependent serotonergic neuromodulation of synaptic strength intrinsic to a central pattern generator circuit.

Neuromodulation is often thought to have a static, gain-setting function in neural circuits. Here we report a counter example: the neuromodulatory effect of a serotonergic neuron is dependent on the interval between its spikes and those of the neuron being modulated. The serotonergic dorsal swim interneurons (DSIs) are members of the escape swim central pattern generator (CPG) in the mollusk Tritonia diomedea. DSI spike trains heterosynaptically enhanced synaptic potentials evoked by another CPG neuron, ventral swim interneuron B (VSI-B), when VSI-B action potentials occurred within 10 sec of a DSI spike train; however, if VSI-B was stimulated 20-120 sec after DSI, then the amplitude of VSI-B synaptic potentials decreased. Consistent with this, VSI-B-evoked synaptic currents exhibited a temporally biphasic and bidirectional change in amplitude after DSI stimulation. Both the DSI-evoked enhancement and decrement were occluded by serotonin and blocked by the serotonin receptor antagonist methysergide, suggesting that both phases are mediated by serotonin. In most preparations, however, bath-applied serotonin caused only a sustained enhancement of VSI-B synaptic strength. The heterosynaptic modulation interacted with short-term homosynaptic plasticity: DSI-evoked depression was offset by VSI-B homosynaptic facilitation. This caused a complicated temporal pattern of neuromodulation when DSI and VSI-B were stimulated to fire in alternating bursts to mimic the natural motor pattern: DSI strongly enhanced summated VSI-B synaptic potentials and suppressed single synaptic potentials after the cessation of the artificial motor pattern. Thus, spike timing-dependent serotonergic neuromodulatory actions can impart temporal information that may be relevant to the operation of the CPG.

Action Potentials↗

PubMed2003

Synaptic gating: the potential to open closed doors.

Synaptic gating is normally thought to be a mechanism for excluding synaptic input, but three recent studies show how the resting membrane potential interacts with integrative properties to act as a permissive synaptic gate.

Animals↗

PubMed2003

G protein signaling in a neuronal network is necessary for rhythmic motor pattern production.

G protein-coupled receptors are widely recognized as playing important roles in mediating the actions of extrinsic neuromodulatory inputs to motor networks. However, the potential for their direct involvement in rhythmic motor pattern generation has received considerably less attention. Results from this study indicate that G protein signaling appears to be integral to the operation of the central pattern generator (CPG) underlying the escape swim of the mollusk Tritonia diomedea. Blocking G protein signaling in a single CPG neuron, cerebral neuron C2, with intracellular iontophoresis of the guanine nucleotide analogue guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S), prevented the production of the swim motor program. Moreover, tonic activation of G protein signaling in this neuron by iontophoresis of the GTP analogues guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) and 5'-guanylyl-imidodiphosphate also inhibited motor pattern production. The possible sites of action of these guanine nucleotide analogues were examined to assess potential mechanisms by which they interfered with motor pattern production. Intracellular iontophoresis of GDP-beta-S into C2 did not affect C2 basal synaptic strength. However, it did reduce heterosynaptic facilitation of C2 synapses caused by the dorsal swim interneurons (DSIs), a set of serotonergic swim CPG neurons. In contrast, GTP-gamma-S directly enhanced C2 synaptic strength onto DFN, mimicking the neuromodulatory effect of the DSIs. GDP-beta-S, but not the GTP analogues, decreased C2 excitability, whereas both GTP analogues, but not GDP-beta-S, blocked the ability of DSI stimulation to increase C2 excitability. The decrease in C2 excitability caused by GDP-beta-S is not likely to be responsible for the inhibition of the swim motor pattern because decreasing C2 firing rate, by injecting hyperpolarizing current, did not prevent the production of the rhythmic motor pattern. Taken together, these data suggest that G protein signaling is a necessary and integral component of the escape swim CPG in Tritonia and that G protein signaling mediates DSI heterosynaptic facilitation of C2 but may not mediate the DSI-evoked enhancement of C2 excitability.

Action Potentials↗