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J Simmers

Publications and source records attributed to J Simmers.

24 records · Page 2Linked to original sources

Dynamic construction of a neural network from multiple pattern generators in the lobster stomatogastric nervous system.

In the stomatogastric nervous system (STNS) of the lobster Homarus gammarus, the rhythmic discharge of a pair of identified modulatory neurons (PS cells) is able to construct de novo a functional network from neurons otherwise belonging to other functional networks. The PS interneurons are electrically coupled and possess endogenous oscillatory properties that can be activated synaptically by stimulation of an identified sensory pathway. PS neurons themselves project synaptically onto the three major neural networks (esophageal, gastric mill, and pyloric) of the STNS. When a PS is rhythmically active in vitro, either spontaneously (rarely) or in response to direct stimulation, it dramatically restructures the otherwise independent activity patterns of all three target networks. This functional reconfiguration elicited by a single cell does not rely on changes in neuronal allegiance to pre-existing circuits, or on a simple merger of these different circuits. Rather, PS is responsible for the creation of an entirely new motor rhythm in that, via its widespread synaptic connections, the interneuron is able to subjugate the ongoing activity of the three STNS circuits and selectively appropriate individual elements to its own intrinsic rhythm. In addition, PS excites motor neurons that innervate dilator muscles of a valve situated between the esophagus and the stomach. The reorganization of the regional foregut motor rhythms by the interneuron is therefore coordinated to the opening of this valve, which itself carries sensory receptors that have been found to activate bursting in PS. Our data suggest that the role of PS in massively restructuring stomatogastric output is to generate a unique motor pattern appropriate for swallowing-like behavior. In a wider context, moreover, the results demonstrate that a neural network may not exist as a predefined entity within the CNS, but may be dynamically assembled according to changing behavioral circumstances.

Animals↗

Tetrodotoxin-sensitive dendritic spiking and control of axonal firing in a lobster mechanoreceptor neurone.

1. A primary mechanosensory neurone, the anterior gastric receptor (AGR) associated with gastric mill muscle in the lobster foregut was examined in vitro with extra- and intra-cellular recording techniques to understand processes of dendritic integration and dendro-axonal communication. 2. AGR has a 'T'-shaped geometry; its two long (> 3 mm) primary dendrites project distally to spatially separate, stretch sensitive terminals and converge centrally onto a common apical neurite that leads to a bipolar soma and single axon. 3. The receptor's bilateral dendrites are independently capable of generating action potentials. These appear to be Na+ dependent since they are blocked by tetrodotoxin, but not by Co2+ or a lack of Ca2+ in the bath saline. 4. Both dendrites are autogenically active, although impulses in the dendrite with the higher intrinsic excitability may cross over and activate the trigger zone on the contralateral side. Moreover, spikes arising on either dendrite do not actively invade the soma, but are conveyed as decremented potentials to a third trigger zone on the initial axon segment. 5. Focal applications of TTX (tetrodotoxin) demonstrated the existence and allowed precise definition of a central membrane compartment of AGR that appears to lack in functional Na+ channels. This inexcitable region includes the soma, the apical neurite and the central branch point of the two dendrites. A failure to observe collision block of bilateral dendritic potentials as they traverse the neurite supported this conclusion. 6. Horseradish peroxidase injections and staining revealed two morphological features of the apical neurite that differed markedly from other regions of the cell. In addition to a relatively large diameter, the neurite's plasma membrane is heavily convoluted and coiled to form a lamellar transverse profile. This latter feature may itself contribute to membrane inexcitability while the former is consistent with an elevated space constant for electrotonic conduction. 7. It is concluded that the inhomogeneous distribution of membrane excitability in AGR enhances the integrative capability of the receptor's dendrites, permitting mechanical input at diverse loci to be encoded and processed prior to transformation into axonal discharge.

Action Potentials↗

Brucella abortus deficient in copper/zinc superoxide dismutase is virulent in BALB/c mice.

The gene encoding the Cu/Zn superoxide dismutase (SOD) of Brucella abortus strain 2308 was identified in a Brucella genomic library utilizing a combination of Western blotting and native gel electrophoresis. The Cu/Zn SOD gene was inactivated in vitro by ligation of a kanamycin resistance gene into the open reading frame encoding SOD. The plasmid born construct was introduced back into B. abortus by electroporation. Replacement of the wild-type Cu/Zn SOD by recombination was demonstrated by showing that both the KnR gene and the Cu/Zn SOD gene hybridized to the same band in a Southern analysis of genomic DNA. In addition, KnR strains were deficient in Cu/Zn SOD activity as assessed by lack of Cu/Zn SOD activity on a native gel and by lack of reactivity with specific serum in a Western analysis. Either strain 2308 or the Cu/Zn SOD deficient mutant injected intraperitoneally into BALB/c mice, exhibited no differences in their ability to colonize the spleen at 7 and 28 days post-inoculation. Thus, the inability to produce Cu/Zn SOD by B. abortus does not significantly impair its virulence in mice.

Animals↗

A disynaptic sensorimotor pathway in the lobster stomatogastric system.

1. In the lobster Homarus, muscle gm 1 that causes protraction of the medial tooth of the gastric mill system is innervated via a dorsal branch of the anterior gastric nerve by motoneurons (GM) arising in the stomatogastric ganglion (STG) (Fig. 1). 2. A ventral branch of the anterior gastric nerve (VAGN) contains a single unit that is mechanosensitive, responds to gentle pressure on the stomach wall in the vicinity of gm 1, and evokes reflex activation of GM motoneurons (Fig. 2). 3. This mechanoreceptor neuron (called anterior gastric receptor, AGR) has been identified morphologically (Fig. 3) and electrophysiologically (Figs. 4 and 5). The bipolar cell body is located in the dorsal ventricular nerve immediately posterior to the STG. It sends out long peripheral processes in the left and right VAGNs to ramify bilaterally in the epidermis of the stomach wall underlying muscle gm 1. The axon of the AGR runs anteriorly through the STG and projects to the left and right commissural ganglia (CoGs) via the stomatogastric (STN) and inferior esophageal nerves. 4. AGR activation of GM motoneurons disappears after cutting the STN, indicating that the reflex is mediated by an axonal pathway involving rostral ganglia (Fig. 6). 5. Electrophysiological (Fig. 7) and morphological (Fig. 8) methods were used to identify an interneuron (commissural gastric neuron, CG) located in each CoG and intercalated between AGR and GM. Axons of the two CGs project to the STG via the superior esophageal nerves and the STN. 6. Simultaneous intracellular recordings from the three cell types demonstrate that AGR excites CG, which in turn excites GM; in each case excitatory postsynaptic potentials follow presynaptic impulses one for one and at constant latency (Fig. 9). Raising the threshold for spiking with saline containing high divalent cation concentrations further indicates that both excitatory connections are monosynaptic and confirms that AGR does not directly excite GM motoneurons (Fig. 10). 7. The input/output properties of AGR in this disynaptic excitatory pathway (Fig. 11) are discussed as also are the functional implications of such a long-loop pathway for sensorimotor integration.

Afferent Pathways↗

Nonlinear interneuronal properties underlie integrative flexibility in a lobster disynaptic sensorimotor pathway.

1. In the lobster Homarus, a single mechanoreceptor neuron (anterior gastric receptor, AGR) associated with muscle gm 1 of the gastric medial tooth has access to motoneurons (GM) innervating this muscle via an excitatory synaptic pathway involving two bilateral interneurons (commissural gastric, CG) (see 31). 2. Studies on in vitro preparations of the stomatogastric nervous system show that despite its apparent simplicity, this disynaptic pathway can express considerable flexibility in information processing, as evident by a wide variety of GM output responses to sensory input from AGR (Fig. 1). 3. This input/output flexibility does not rely on multiple synaptic pathways operating in parallel with the interneuron CG, since it is demonstrated that AGR has access to GM only via CG (Fig. 2). 4. Short AGR impulse trains at different spike frequencies can give rise to similarly brief excitation of GM, or prolonged motoneuron responses. Moreover, graded increases in AGR discharge frequency can lead to a sudden increase in the intensity of GM responsiveness that otherwise grades linearly with receptor firing. Such step changes in gain (both in duration and magnitude) are due to synaptic triggering of regenerative "plateau" depolarizations in CG (Figs. 3 and 4). 5. Sustained tonic discharge in AGR can induce cyclic bursting activity in previously nonrhythmic GM neurons. Furthermore, the frequency of motoneuron bursts increases with the frequency of AGR tonic firing. Such changes in pattern are ascribed to synaptic triggering and modification of regenerative "oscillatory" depolarizations in CG (Fig. 5). 6. Higher levels of AGR firing can result either in strong activation of GM motoneurons or in complete inactivation of GM. This switch in sign of the motor response is dependent on base-line levels of activity in the receptor and is due to the capability of CG to fire action potentials only within a window of membrane potential (Figs. 6-8). The functional outcome of this cellular property of CG is that positive feedback from AGR to GM can be switched to negative feedback via the same excitatory synaptic pathway (Fig. 9). 7. We conclude that flexibility in sensorimotor integration can be an inbuilt feature even of hard-wired neuronal pathways; in the present case, changes in input/output relationships reside with intrinsic properties of an intercalated interneuron (Fig. 10).

Action Potentials↗