James S. Schwaber

Abolition of the behavioral effects of cholecystokinin following bilateral radiofrequency lesions of the parvocellular subdivision of the nucleus tractus solitarius.

Cholecystokinin (CCK) has been implicated as a signal for the syndrome of satiety in a variety of species. Several lines of evidence point to a peripheral site of action for the behavioral effects of CCK. Peripheral CCK receptors appear to activate a gut-brain pathway involving the sensory fibers of the vagus nerve. To investigate the central anatomical substrate of this visceral-behavioral control system, the terminal regions of the sensory tract of the vagus were lesioned. Selective destruction of the parvocellular subdivisions of the nucleus tractus solitarius (NTS) blocked the effects of acute doses of CCK on exploratory behaviors. Sham lesions and lesions destroying only the remaining regions of the NTS or the vagal motor nuclei had no effect on baseline exploratory behaviors and did not influence the ability of CCK to decrease spontaneous exploratory behaviors. These findings delineate the first central site along the ascending sensory pathway which appears to mediate the satiety-related behavioral effects of CCK.

A dynamic neural network approach to nonlinear process modeling

Abstract The use of feedforward neural networks for process modeling has proven very successful for steadystate applications, but suitable applications for dynamic systems are still being studied. A novel approach is presented in this paper which uses intrinsically dynamic neurons inspired from biological control systems as the processing elements in network architectures. This results in a network which incorporates dynamic elements with continuous feedback. Two case studies show that the recurrent dynamic neuron network (RDNN) does an excellent job of predicting nonlinearities such as asymmetric dynamic response. In addition, the RDNN significantly outperforms linear models and more traditional neural network models for open-loop simulations. Finally it is shown how this RDNN model can be used in model-based control architectures, such as internal model control.

Somatostatinergic projections from the central nucleus of the amygdala to the vagal nuclei

In the rat, somatostatin immunoreactivity was identified in neurons of the central nucleus of the amygdala that were retrogradely labeled by injection of fluorescent dyes into the nucleus tractus solitarius and dorsal motor nucleus of the vagus nerve. The double-labeled neurons are located in the medial subdivision of the central nucleus and appear to comprise less than one fifth of the descending pathway. These results suggest that somatostatin may act as a neurotransmitter in a pathway which mediates cardiovascular and other autonomic responses to fear-producing and other emotional stimuli.

Characteristic firing behavior of cell types in the cardiorespiratory region of the nucleus tractus solitarii of the rat

The present in vitro study was performed to characterize neurons within dorsal regions of the nucleus tractus solitarii (NTS), principally at the level of area postrema, and known to receive inputs predominantly from cardiovascular and respiratory afferents (i.e. cardiorespiratory NTS). This report describes 4 classes of neurons (S1-S4) that were silent at their resting membrane potential and received relatively short (< 3.6 ms) and consistent latency synaptic inputs (+/- 0.4 ms) comprising either an EPSP or EPSP/IPSP sequence following low intensity electrical stimulation of the solitary tract (ts). Intracellular recording with sharp electrodes were used to characterize neuron types based on their different firing response patterns to injection of depolarizing current. S1 cells showed a single action potential; S2 fired repetitively; S3 produced a 2-5 spike burst coincident with the start of the current pulse and S4 neurons showed delayed excitation. Accommodation of firing frequency was seen in S2, S3 and some S4 cells. The voltage dependency of the different discharge patterns of the 4 cell groups was tested by current pulse stimulation at different holding potentials. However, in the majority of cells in any one cell class the firing pattern was qualitatively similar. Based on these findings it is suggested that the different firing characteristics reflect differences in intrinsic membrane properties between neuron classes. Representative examples from each of the defined cell classes were further studied in current and voltage clamp using the whole cell patch technique to define the presence and role of certain ionic currents in the firing response patterns of the 4 cell groups. In the current clamp configuration the firing behavior of S1 neurons (single spiking) was unaltered during exposure to 4-aminopyridine (4-AP; 2 mM), cobalt chloride (Co; 5 mM), norepinephrine (NE; 20 microM) and muscarine chloride (50 microM). It is suggested that the relatively low excitability of this neuron is due a persistent outward current which occurred at -40 mV during depolarizing voltage steps in the voltage clamp configuration. A common characteristic of S2 neurons (repetitively firing) was that they showed accommodation during current injection which was greatly attenuated in the presence of Co or NE. In addition, 4-AP slowed the firing frequency, reduced the afterhyperpolarization and broadened the spike width of S2 cells. Interestingly, the amount of accommodation observed in S2 cells was variable for cells of this class and was proportional to the magnitude of a Co-sensitive inward current present during depolarizing voltage steps between -45 to -5 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Nucleus tractus solitarius lesions block the behavioral actions of cholecystokinin

Cholecystokinin (CCK) has been implicated as a signal for the syndrome of satiety in a variety of species. Several lines of evidence point to a peripheral site of action for the behavioral effects of CCK. Peripheral CCK receptors appear to activate a gut-brain pathway involving the sensory fibers of the vagus nerve. To investigate the central anatomical substrate of this visceral-behavioral control system, the terminal regions of the sensory tract of the vagus were lesioned. Radiofrequency lesions of the nucleus tractus solitarius abolished the effects of acute doses of CCK on exploratory behaviors. Sham lesions had no effect on baseline exploratory behaviors and did not influence the ability of CCK to decrease spontaneous exploratory behaviors. These findings delineate the first central site along the ascending sensory pathway which appears to mediate the satiety-related behavioral effects of CCK.

Dynamic gain scheduled process control

Abstract Gain scheduled control techniques are widely used in the chemical and aerospace industries but suffer from the limitation to slowly changing scheduling variable (ξ). A dynamic gain scheduling (DGS) algorithm is proposed to specifically address this constraint. The control synthesis is based on algebraic transformations of the composite nonlinear controller obtained using the input–output linearization (IOL) and internal model control (IMC) formalisms. The controller is reduced to linear form and implemented in a dynamic gain scheduling approach, scheduled in the two-dimensional ξ and ξ space. In this fashion, the time variation of the scheduling variable is explicitly accounted for. The algorithm is demonstrated on a simple isothermal continuous stirred tank reactor and a complex, highly nonlinear low-density polyethylene polymerization reactor. Simulation results for the polymerizer case study show that the DGS controller provides satisfactory control during polymer grade changes, outperforms IOL control for disturbance rejection, and is stable under noisy measurements. Performance under parametric uncertainty as well as uncertainty with respect to unmodeled dynamics is also evaluated. Structured singular value analysis for nonlinear and time-varying uncertainty facilitated the determination of theoretical stability of the DGS loop. Finally, extensions to multiple-input–multiple-output systems and systems with higher relative degrees are discussed.

Neuroanatomical Substrates of Cardiovascular and Emotional — Autonomic Regulation

During the past decade a specific group of brain nuclei has come to be seen as important in the central neuronal regulation of the circulation. These highly interconnected nuclei have gained prominence principally because of their relationship to the nucleus tractus solitarii (NTS) and autonomic preganglionic neuronal populations in the dorsal motor nucleus of the vagus nerve (DMN), nucleus ambiguus (NA) and spinal cord. Using modern tract-tracing methods, investigators have mapped the central connections of these visceral sensory and autonomic nuclei and delineated the network of cell groups illustrated in Fig. 1. In addition, immunochemical techniques have provided biochemical information indicating an abundance of peptides and other neurotransmitters within these cell groups. As a consequence of these findings, a picture of the cellular basis for central cardiovascular regulation is emerging.

Quantitation of cellular resolution in situ hybridization histochemistry in brain by image analysis

A new method for relative quantitation of mRNA levels with single neuron resolution is described. Hybridized tissue sections are emulsion dipped, exposed, and developed. The resulting silver grains are visualized using dark-field microscopy at high magnification. The method relies on computer-based image analysis of sequentially located, high resolution, small fields containing the cell images, each of which is analyzed for mRNA content. Maps of cell distributions are constructed, with cell marks color-coded for relative mRNA levels, yielding previously unavailable information on regional distribution of quantitative cellular expression of specific mRNA in brain.

The ventrolateral medulla as a source of synaptic drive to rhythmically firing neurons in the cardiovascular nucleus tractus solitarius of the rat

We sought to determine whether the caudal ventrolateral medulla (cVLM), at the level of area postrema, influences the rhythmically beating neurons found within the dorsomedial NTS in rat brainstem slices. Intra- or extracellular recordings of neurons firing rhythmically at around 5 Hz were characterized as either auto-active (i.e. pacemaker; AA) or synaptically driven (SD) by pharmacological interventions. The nature of inputs evoked from the ipsilateral cVLM were orthodromic and the majority were excitatory (latency 3-20 ms). Further, this excitatory influence was found to be tonically active in 25/47 cells studied since inactivating the ipsilateral cVLM by localized cooling reduced the firing rate by 0.5-3.0 Hz (23% on average). Neuronal characterization showed that the most consistent and pronounced effect occurred on SD rather than AA cells. Control experiments that cooled other areas of the slice closer to the recording site proved ineffective. Additional studies showed that most rhythmically firing cells in the NTS received an excitatory synaptic input from the solitary tract (ts; latency 3-30 ms). This input was reduced or blocked by inactivating the cVLM in neurons in which the ts latency of activation was greater than 8 ms in half of the neurons tested. Subsequent pharmacological tests revealed that these neurons were predominantly SD. Identified AA neurons received an input from the ts at a shorter latency, typically less than 8 ms, and this was unperturbed by cooling the cVLM in all cases. Further, there was no obvious difference in the baseline discharge rates between cells in the hemi-slice and those recorded in an intact slice. In a hemi-coronal slice cooling the cVLM also produced a 20% decrease in firing rate in identified SD neurons but no consistent change in AA cells. We conclude that (1) the ipsilateral cVLM contributes principally tonic excitatory drive to rhythmically active neurons in the dorsomedial NTS in vitro and this preferentially effects SD neurons; (2) other excitatory drives other than those from the ipsilateral cVLM impinge upon SD cells, the origin of which are relatively local and likely to be in the NTS; (3) in the slice the projection from the cVLM to the NTS appears to be present but the reciprocal connection is absent.

Quantitation and digital representation of in situ hybridization histochemistry

Publisher Summary In situ hybridization histochemistry has frequently been used as a qualitative technique to detect and localize specific nucleic acid sequences in an anatomical context, without particular respect to the abundance of the detected sequence. Quantitative analysis is necessary for evaluating changes in gene expression with in situ hybridization histochemistry. The structural and functional complexity of the brain requires that this analysis be represented in an anatomical context to be meaningful. With autoradiographic film analysis, this process is efficiently carried out by the computerized densitometry and pseudocolor representation of the film images of the hybridization signal. In contrast, a quantitative analysis of autoradiographic grain density at the cellular level is more difficult. However, the high degree of anatomical specificity and resolution obtained with emulsion autoradiography should facilitate any study of the distribution and regulation of messenger RNA (mRNA) levels in heterogeneous tissues, such as the brain.