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Novel interneuronal network in the mouse posterior piriform cortex.

The neural circuits of the piriform cortex mediate field potential oscillations and complex functions related to integrating odor cues with behavior, affective states, and multisensory processing. Previous anatomical studies have established major neural pathways linking the piriform cortex to other cortical and subcortical regions and major glutamatergic and GABAergic neuronal subtypes within the piriform circuits. However, the quantitative properties of diverse piriform interneurons are unknown. Using quantitative neural anatomical analysis and electrophysiological recording applied to a GAD65-EGFP transgenic mouse expressing GFP (green fluorescent protein) under the control of the GAD65 promoter, here we report a novel inhibitory network that is composed of neurons positive for GAD65-EGFP in the posterior piriform cortex (PPC). These interneurons had stereotyped dendritic and axonal properties that were distinct from basket cells or interneurons expressing various calcium-binding proteins (parvalbumin, calbindin, and calretinin) within the PPC. The GAD65-GFP neurons are GABAergic and outnumbered any other interneurons (expressing parvalbumin, calbindin, and calretinin) we studied. The firing pattern of these interneurons was highly homogenous and is similar to the regular-spiking nonpyramidal (RSNP) interneurons reported in primary sensory and other neocortical regions. Robust dye coupling among these interneurons and expression of connexin 36 suggested that they form electrically coupled networks. The predominant targets of descending axons of these interneurons were the dendrites of Layer III principal cells. Additionally, synapses were found on dendrites and somata of deep Layer II principal neurons and Layer III basket cells. A similar interneuronal subtype was also found in GAD65-EGFP-negative mouse. The extensive dendritic bifurcation at superficial lamina IA among horizontal afferent fibers and unique axonal targeting pattern suggests that these interneurons may play a role in direct feedforward inhibitory and disinhibitory olfactory processing. We conclude that the GAD65-GFP neurons may play distinct roles in regulating information flow and olfactory-related oscillation within the PPC in vivo.

Animals↗

An intact glutamatergic trigeminal pathway is essential for the cardiac response to simulated diving.

Nasal water flow plus concomitant expiratory apnea in anesthetized (Innovar-Vet), paralyzed, and artificially ventilated rats produces immediate bradycardia. To investigate the origin of this response, four procedures were used to block the trigeminal pathway. 1) Trigeminal receptors within the nasal passages were anesthetized by infusing local anesthetic through the external nares. 2) Trigeminal nerves that innervate the nasal passages were sectioned bilaterally as they passed through the orbit. 3) The trigeminal neural pathway was blocked within the brain stem by either electrolytically lesioning or infusing local anesthetic into the spinal trigeminal nucleus interpolaris (Sp5I). 4) Synaptic transmission within Sp5I was prevented by infusing glutamate receptor antagonists D-2-amino-7-phosphonoheptanoic acid and 6,7-dinitroquinoxaline-2,3-dione. After each of the procedures was completed, the cardiovascular responses to nasal water flow plus apnea were either attenuated or eliminated. The major conclusion of this study is that an intact glutamatergic trigeminal pathway is required for manifestation of the cardiovascular responses to nasal stimulation. Evidence also suggests that N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors are both required for synaptic neurotransmission within Sp5I.

Animals↗

Cholinergic limbic projections and behavioral role of basal forebrain nuclei in the rat.

The purposes of the present study were to identify cholinergic non-neocortical projections of the basal forebrain and to determine the role of this region in the regulation of estrogen-dependent reproductive behaviors in the rat. Bilateral electrolytic lesions were placed in an area encompassing the horizontal limb of the diagonal band, as well as portions of the substantia innominata and magnocellular preoptic nucleus, and choline acetyltransferase (CAT) activity was assayed in microdissected brain areas seven days after lesion. Compared to sham surgery, lesions of this region significantly reduced CAT activity in the basal amygdala (34%), dorsal hippocampus (14%), cingulate cortex (25%), piriform cortex (36%), and entorhinal cortex (34%). Other limbic and midbrain structures do not appear to receive significant cholinergic innervation from this locus since no reductions in CAT were detected after bilateral lesions. These included the anterior hypothalamus, ventromedial hypothalamus, mammillary nucleus, habenula, subiculum, ventral hippocampus, insular cortex, central gray, and interpeduncular nucleus. Behaviorally, female rats with bilateral lesions of the basal forebrain displayed an unusually high incidence of rejection behavior in response to attempted mounts by stimulus male rats in sexual behavior tests. There was no effect of basal forebrain lesions on the incidence of lordosis exhibited by these females. The dissociation of rejection and lordosis suggests that distinct neural pathways mediate the occurrence of these reproductive behaviors and that rejection behavior may be regulated by basal forebrain pathways.

Animals↗

Effects of frontal eye field and superior colliculus ablations on eye movements.

Two parallel neural pathways are primarily responsible for the control of saccadic eye movements--one mediated through the frontal eye fields and the other through the superior colliculus. When both pathways are disrupted, control of saccadic eye movements is lost. Disruption of either pathway alone produces only subtle deficits.

Animals↗

[An electrophysiological analysis of pathways from lateral septum to hippocampal CA1 area in rat].

Upon stimulating the lateral septal region, a population spike could be recorded in the stratum pyramidale of hippocampal CA1 together with a recordable EPSP in the apical dendrites (stratum radiatum). After destruction of hippocampal CA3, CA4 pyramidal cells by intraventricular microinjection of kainic acid, electrical stimulation of the lateral septum could no longer evoke EPSP in the apical dendrites. This experiment suggests that the neural connection of the lateral septo-CA1 apical dendrites is mediated by the collaterals of the ipsilateral CA3 pyramidal cells. But after the destruction of CA3, CA4, electric stimulation of lateral septum could still evoke EPSP in the basal dendrites (stratum oriends). The neural connection mediating the response of the lateral septo-CA1 basal dendrites was not reported before, but the neural pathway remains to be investigated.

Animals↗

Central and feedback regulation of hypothalamic corticotropin-releasing factor secretion.

Physical, emotional and metabolic stressors activate the hypothalamo-pituitary-adrenal (HPA) axis via multiple neural pathways. Final hypothalamic coding of stressor-induced adrenocorticotropic hormone (ACTH) secretion is mediated by differential release of ACTH secretagogues. These include, but may not be limited to, corticotropin-releasing factor (CRF), arginine vasopressin, oxytocin and, possibly, adrenaline. Among these substances, CRF serves as the predominant regulatory factor of this axis because its presence is obligatory for the action of intrinsically weaker secretagogues. Because neural input-encoding qualities of individual stressors utilize, in part, stimulus-specific pathways, the effectiveness of glucocorticoid negative feedback in modulating ongoing and subsequent activity of the HPA axis is dependent upon the type of stressor and the nature of the neural pathways mediating the initial activity. Studies suggest that responses to physical stressors (for example, haemorrhage) are resistant to classical intermediate feedback, whereas those to emotional/cognitive stressors (such as a novel environment) are strongly susceptible to feedback. Overall functional characteristics of the HPA axis in adult organisms are at least partially a result of neonatal experience. In the adult differences in hypothalamic CRF mRNA levels, median eminence peptide content and pituitary responsiveness to stressors can be correlated with aspects of neonatal experience.

Animals↗

Scotopic sensitivity to ON and OFF stimulus transients.

The luminance of a large diffuse field, viewed peripherally, was temporally modulated near absolute detection threshold. The field luminance either increased abruptly and decreased gradually (ON stimulus) or increased gradually and decreased abruptly (OFF stimulus). For all wavelengths shorter than 620 nm, sensitivity to the ON stimulus was greater than to the OFF. The spectral sensitivity curves obtained indicate that rods and/or their associated neural pathways are more sensitive to ON stimulus transients than to OFF.

Adult↗

Pathways mediating abdominal phasic flexor muscle activity in crayfish with chronically cut nerve cords.

1. Nerve cord transection abolishes the ability of crayfish (Procambarus clarkii) to produce tailflips in response to gradually applied tactile or proprioceptive stimulation of the abdomen, but this ability eventually returns. To determine the time-course of this return and to analyze its underlying neural pathways, we made behavioral observations, electromyographic recordings from abdominal phasic flexor muscles, and intracellular recordings from motoneurons in crayfish with cord lesions between the thorax and the abdomen. 2. Abdominal stimulation activated the phasic flexor muscles in the rostral 5 abdominal segments and their homologs in the 6th segment, the posterior telson flexor muscles. Nearly one-quarter of cord-transfected animals responded to the stimuli with phasic flexor muscle activity by one week after the lesion, and almost 90% were responsive by 3 weeks. 3. Regeneration of axons across the lesion played little or no role in the recovery of phasic flexor muscle responsiveness. In addition, the lateral giant axons were not activated by the gradually applied stimuli that triggered phasic flexor muscle contractions. These results suggest that non-giant pathways confined to the abdominal nervous system become functional following chronic cord transection. 4. Retransection of the nerve cord below the original lesion showed that smaller subsets of the abdominal cord, including a single ganglion, could develop the ability to generate phasic flexor muscle contractions in response to gradually applied stimuli. 5. Phasic flexor motoneurons in cord-transected animals could be excited by stimulation of afferents throughout the abdomen. The sensory pathways producing this activation appear to project through the nerve cord without much cross-over between left and right sides.

Abdominal Muscles↗

Physiology of somatosensory and estrogenic control over the lordosis reflex.

The simplest mechanism for lordosis behavior, as allowed by the present data, is as follows. Estrogen acts on the ventromedial nucleus of hypothalamus (VMN) to induce a tonic facilitatory output, which is relayed by neurons in mesencephalic central gray and then the medullary reticulospinal tract to the spinal cord. To trigger the lordosis reflex, sensory inputs from cutaneous touch-pressure receptors located in rump-perineal skin are required. Neural pathways exist for transmitting these inputs to motor neurons in the spinal cord and to certain supraspinal locations, but our electrophysiological studies indicate that the most likely place where these sensory inputs interact with estrogen-influenced neural activity to elicit the reflex is the spinal cord itself.

Animals↗

Dissociating the roles of the rostral anterior cingulate and the lateral prefrontal cortices in performing two tasks simultaneously or successively.

A fundamental question about the nature of cognitive control is whether performing two tasks successively or simultaneously activates distinct brain regions. To investigate this question, we designed a functional magnetic resonance imaging (fMRI) study that compared task-switching and dual-task performance. The results showed that performing two tasks successively or simultaneously activated a common prefronto-parietal neural network relative to performing each task separately. More importantly, we found that the anterior cingulate and the lateral prefrontal cortices were differently activated in dual-task and task-switching situations. When performing two tasks simultaneously, as compared to performing them in succession, activation was found in the rostral anterior cingulate cortex. In contrast, switching between two tasks, relative to performing them simultaneously, activated the left lateral prefrontal cortex and the bilateral intra-parietal sulcus region. We interpret these results as indicating that the rostral anterior cingulate cortex serves to resolve conflicts between stimulus-response associations when performing two tasks simultaneously, while the lateral prefrontal cortex dynamically selects the neural pathways needed to perform a given task during task switching.

Adult↗

Direct neuronal projection from the dorsal raphe nucleus to the pineal complex of the rat: a Phaseolus vulgaris-leucoagglutinin in vivo neuronal tracing study.

By use of Phaseolus vulgaris-leucoagglutinin as an anterograde in vivo tracer, a direct projection from the dorsal raphe nucleus to the pineal complex of the rat was demonstrated. The nerve fibers extended from the dorsal raphe nucleus rostrally through the mesencephalic periaqueductal grey and entered the deep pineal from both the posterior commissure and the habenular area. A dense innervation of the deep pineal and the pineal stalk was observed, but the nerve fibers were not observed to enter the superficial pineal gland. This new neural pathway might connect the visual system with the pineal complex of the rat.

Animals↗

[3H]DPDPE binding to delta opioid receptors in the rat mesocorticolimbic and nigrostriatal pathways is transiently increased by acute ethanol administration.

Dopaminergic transmission in the mesolimbic and nigrostriatal pathways plays a key role in the reinforcement mechanisms and brain sensitivity to ethanol, respectively. Ethanol reinforcement and high alcohol drinking behaviour have been postulated to be partially mediated by a neurobiological mechanism involving the ethanol-induced activation of the endogenous opioid system. Activation of opioid neural pathways by ethanol may include alterations in the processing, release and/or the receptor binding of opioid peptides. The aim of this work was to investigate the effects of acute ethanol administration on delta opioid receptors in the rat mesocortical, meso-accumbens and nigrostriatal pathways by quantitative receptor autoradiography, using [(3)H] (2-D-penicillamine, 5-D-penicillamine)-enkephalin as radioligand. A significant increase in [(3)H] (2-D-penicillamine, 5-D-penicillamine)-enkephalin binding was observed in the substantia nigra pars reticulata 1 h after ethanol treatment. Two hours after drug exposure, ligand binding was significantly increased in the frontal and prefrontal cortices, the core and shell regions of the nucleus accumbens, and in the anterior-medial and medial-posterior regions of the caudate-putamen. In contrast, ligand binding was significantly decreased in the posterior region of the caudate-putamen 30 min after ethanol administration. The observed effects may reflect ethanol-induced changes in ligand binding affinity and/or in receptor density. Our results suggest that transitory changes in delta opioid receptors with different kinetic patterns may be involved in ethanol reinforcement and brain sensitivity to the drug. Ethanol-induced delta receptor up- and down-regulation mechanisms may participate in modulation of dopaminergic transmission in the mesocorticolimbic and nigrostriatal pathways.

Analgesics, Opioid↗

Diagnostic conclusions from computerized smooth pursuit tracking data.

Measures of phase (lead or lag of target), gain (amplitude of response), and spectral purity (distortion of smooth tracking) were obtained by a cross-power spectral analysis of the stimulus input and the eye movement output. Normal patients showed no central involvement of the pursuit pathways in the central nervous system. Patients with central lesions had marked deficits. At this time it is premature to try to localize the site of lesion on the basis of these raw data. A small sample of known diagnoses have been chosen to evaluate this tracking system. Hopefully, this method will contribute to a better understanding of the neural pathways of vestibulo-oculomotor function and provide diagnostic information.

Cerebellar Diseases↗

Giant neuron pathway neurophysiological activity in per(0) mutants of Drosophila melanogaster.

In Drosophila melanogaster, the clock gene period (per) has a clearly defined role in the molecular machinery involved in generating free-running circadian rhythms. per mutations also influence rhythms in the Drosophila love song and in the ultradian timescale. The relationship between these two phenomena has so far escaped satisfactory explanation. Here we analyzed the neurophysiological activity of the giant fiber neural pathway in per(0) flies. Under constant light, and at relatively low stimulation frequencies (1-2 Hz), per(01) flies habituate significantly earlier than they do under 12 h light-dark cycles. The results suggest an involvement of per in phenomena of short-term neural plasticity.

Adaptation, Physiological↗

Characterization of vagal pathways mediating gastric accommodation reflex in rats.

1. We investigated the vagal pathways mediating the gastric accommodation reflex in the rat stomach. 2. Gastric distension (6 ml) evoked an increase of 9.0 +/- 1.0 cmH2O of intragastric pressure in vivo. Pretreatment with tetrodotoxin (TTX) caused a significant pressure increase by gastric distension, reaching 17.0 +/- 1.7 cmH2O, suggesting mediation by neural pathways. 3. The pressure increase evoked by gastric distension was significantly enhanced in vivo by acute truncal vagotomy (TV), hexamethonium (C6), and NG-nitro-L-arginine methyl ester (L-NAME), but not by vasoactive intestinal polypeptide (VIP) antiserum, guanethidine, or splanchnicotomy. 4. Gastric distension (6 ml) evoked a much larger intragastric pressure in the denervated, vascularly isolated, perfused rat stomach in vitro. Intra-arterial application of TTX and L-NAME did not cause further pressure increases evoked by gastric distension. 5. The pressure increase evoked by gastric distension remained high 2 weeks after TV in vivo. However, the accommodation reflex was fully restored 4 weeks after TV in vivo. This reflex was antagonized by TTX, C6 and L-NAME, but not by VIP antiserum, guanethidine and splanchnicotomy. 6. Similar to in vivo studies, gastric distension caused a smaller increase in intragastric pressure in response to gastric distension in the denervated, vascularly isolated, perfused stomach obtained from rats 4 weeks after vagotomies in vitro. The pressure increase evoked by gastric distension was significantly enhanced by L-NAME, hexamethonium and TTX. 7. It is suggested that the vago-vagal reflex plays an important role in mediating the accommodation reflex. This involves a vagal efferent pathway that uses nitric oxide as a final neurotransmitter mediating gastric relaxation in intact rats. It is also suggested that the adaptive mechanism mediating the accommodation reflex following vagotomy occurs in the gastric myenteric plexus.

Adaptation, Physiological↗

Opiate nerves mediate feline pyloric response to intraduodenal amino acids.

Intraluminal pressures and myoelectric activity were recorded from the feline antrum, pylorus, and duodenum in response to intraduodenal amino acid solutions. Mixed amino acids (0.02 mg/ml, 3.0 ml) increased the amplitude of pyloric contractions (59.7 +/- 7.9 mmHg) and pyloric spike activity (73.7 +/- 6.8% of slow waves with spike activity) compared with a saline control (P less than 0.001). The selectivity of these responses was determined with specific amino acids. L-Tryptophan (10 or 40 mM) produced a response similar to the mixed amino acid response, while L-phenylalanine or L-glycine (10 or 40 mM) had no effect. Intra-arterial tetrodotoxin, intraluminal ethyl aminobenzoate, or intravenous naloxone (1.0 mg/kg) abolished the pyloric responses to amino acids (P less than 0.02). Bilateral cervical vagotomy had no effect. Cholecystokinin octapeptide (CCK-OP) produced dose-dependent increases in the amplitude of pyloric contractions and in pyloric spike activity. The ED50 dose of CCK-OP (1.0 microgram/kg iv) gave an increase in pyloric pressure of 155.6 +/- 49.9 mmHg and in spike activity of 77.7 +/- 9.4%, similar to mixed amino acids or tryptophan. These effects of CCK-OP were not antagonized, however, by a dose of naloxone (1.0 mg/kg) that blocked the maximal pyloric response to leucine-enkephalin. We concluded intraduodenal mixed amino acids or tryptophan increase phasic, spike-dependent pyloric contractions in the cat via nonvagal, naloxone-sensitive neural pathways, phenylalanine, a structurally similar essential amino acid, had no effect on the feline gastroduodenal junction, and the pyloric responses to exogenous CCK-OP are mediated by pathways distinct from the responses to tryptophan or mixed amino acids.

Amino Acids↗

A method for the determination of projection areas of GABA immunoreactive neurons in the invertebrate nervous system.

Axonal transport of metallic salts (nickel or cobalt chloride) has been widely used for the anatomical mapping of neural pathways. We show here that when nickel is introduced into GABAergic neurons it completely eliminates GABA immunolabelling. We have used this property to determine the axonal projections of GABAergic neurons in the stomatogastric system of Crustacea. For example, following nickel backfills from either cut axons or from terminals, GABA immunostaining labels only those GABA-immunoreactive neurons which had not been retrogradely labelled with nickel and hence did not project in the cut nerve or to the neuropile uptake site. By comparing such immunolabelled preparations with those not pretreated with nickel the projection patterns of all the GABA immunoreactive neurons in a given system can be revealed. This effect of nickel appears to be selective for GABA immunostaining, insofar as it does not interfere with the immunodetection of either the peptide proctolin or a FMRFamide-like peptide. This method may prove to be a useful tool for analyzing GABAergic neuronal pathways in the nervous systems of invertebrates.

Animals↗