A study of neuronal circuitry mediating the saccadic suppression in the rabbit

Summary Stimulation of the deep layers of the superior colliculus (SC) evoked an IPSP in the relay cells of the lateral geniculate nucleus (LGN). The latency of the JPSP ranged from 3.3 to 4.7 ms with an average of 3.87±0.56 ms (S.D.). The IPSP from SC stimulation was proposed to be mediated by the recurrent inhibitory circuit to LGN, since the recurrent inhibitory interneurones in the thalamic reticular nucleus (R) responded to the same stimulation with a latency of 2.14±0.43 ms, which was 1.73 ms shorter than the latency of the IPSP in LGN relay cells. This was in good agreement with our previous observation that the recurrent interneurones always fired about 1.8 ms prior to the onset of the recurrent IPSP in LGN (Lo and Xie 1987b). The recurrent inhibitory interneurones could also be excited by stimulation of the central lateral nucleus (CL) with a very short latency (0.57±0.15 ms), suggesting a monosynaptic connection between the central lateral nucleus and the reticular recurrent interneurones. This suggestion was supported by the fact that CL neurones, which projected to the striate cortex (Cx), were antidromically excited by stimulation of the caudal part of R where the recurrent inhibitory interneurones were situated. CL neurone's response to stimulation of the deep layers of SC (SC-CL response) has a latency of 1.68±0.56 ms, which was comparable with the difference between the latency of SC-R response and that of CL-R response, just as expected from the notion that the saccadic suppression is mediated by a circuit of SC (deep layers) -CL-R-LGN.     

Classical conditioning of the flexion reflex in spinal cat: features of the reflex circuitry

A technique has been developed to investigate sodium-independent L-[3H]glutamate binding in rat brain sections using quantitative autoradiography and tritium-sensitive film. Binding is rapid (reaching equilibrium in 5 min) and reversible (having a t 1/2 of dissociation of 0.38 min). Glutamate apparently bound to a single population of sites with a Kd of about 1.0 microM. The pharmacology of this binding site is similar to that observed in homogenate studies. There is marked regional variation in the amount of glutamate bound. Of the areas analyzed in detail, the density of sites is greatest in stratum moleculare of hippocampus, followed by striatum and cortex.     

An analysis of possible nervous mechanisms involved in the peristaltic reflex

1. The effects of drugs on peristalsis and on the contractions of the two muscle coats of the isolated guinea-pig ileum in response to co-axial electrical stimulation have been studied.2. Co-axial stimulation (0.1 msec pulses) never produces simultaneous contraction of both muscle coats. When one muscle contracts, the other either relaxes or remains quiescent.3. The circular muscle contraction has two components. The first is reflex in origin and is brought about either by distension of the gut with increasing intraluminal filling or by the contraction of the longitudinal muscle in response to electrical stimulation at low frequency (1/sec), provided this raises the intraluminal pressure to the threshold for eliciting the circular muscle contraction. As the circular muscle contracts, the longitudinal muscle relaxes although stimulation continues. If the circular muscle contraction is prevented by reducing the intraluminal filling, or by adding a ganglion-blocking drug, the longitudinal muscle remains contracted until withdrawal of the stimulus.4. In the presence of hyoscine, the reflex contraction of the circular muscle is unimpaired but, since the longitudinal muscle contraction is abolished, a higher intraluminal pressure is required to elicit the reflex.5. The second component of the circular muscle contraction appears in response to electrical stimulation at high frequency (3-10/sec), upon withdrawal of electrical stimulation. This delay indicates the simultaneous stimulation of a dominant inhibitory innervation.6. The excitatory nerves to the circular muscle require a higher frequency of stimulation than those to the longitudinal muscle, which respond to single shocks.7. Cholinergic blocking agents (hyoscine, morphine, hemicholinium and botulinum toxin) antagonize the responses of the longitudinal muscle to co-axial stimulation without affecting those of the circular muscle, thus suggesting that the excitatory fibres to the circular muscle are not cholinergic. Prostaglandins (E(1) and E(2)) selectively antagonize the circular muscle contractions evoked by co-axial stimulation. Tetrodotoxin blocks both longitudinal and circular muscle responses.8. Dimethylphenylpiperazinium (DMPP) and 5-hydroxytryptamine (5-HT) stimulate ganglia but have no direct action on the smooth muscle of guinea-pig ileum.9. During a maintained contraction of the longitudinal muscle in the presence of high concentrations of acetylcholine (2.5 x 10(-7) to 10(-6) g/ml.) a contraction of the circular muscle accompanied by a relaxation of the longitudinal muscle is elicited by distension of the gut, and by co-axial stimulation. Similar reciprocal responses are produced by 5-HT or by DMPP and they are finally blocked by DMPP.10. These results are consistent with the hypothesis that in the myenteric plexus there exists an arrangement of nerves which ensures that the two muscle coats of the intestine do not contract simultaneously but are activated reciprocally so that when one muscle layer contracts the other relaxes or is prevented from contracting.     

Organization of the neural switching circuitry underlying reflex micturition

The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain and spinal cord that coordinates the activity of the bladder and urethral outlet. Experimental studies in animals indicate that urine storage is modulated by reflex mechanisms in the spinal cord, whereas voiding is mediated by a spinobulbospinal pathway passing through a coordination centre in the rostral brain stem. Many of the neural circuits controlling micturition exhibit switch‐like patterns of activity that turn on and off in an all‐or‐none manner. This study summarizes the anatomy and physiology of the spinal and supraspinal micturition switching circuitry and describes a computer model of these circuits that mimics the switching functions of the bladder and urethra at the onset of micturition.     

An excitatory body-antral reflex in the sheep abomasum.

This paper describes an abomasal body-antral excitatory reflex in acute experiments in sheep anaesthetized with chloralose. The abomasum was either surgically intact or acutely transected to form separate compartments of the abomasal body and antrum. Inflation of a balloon situated in the abomasal body and active contraction of the abomasal body increased the amplitude of antral contraction. In the intact preparation, inflation of the abomasal body increased the amplitude of antral contraction before and after extrinsic denervation. The antral response was reduced by 75% after extrinsic denervation. In the acutely transected preparation, inflation of the abomasal body and electrically induced contraction of the abomasal body also increased antral contraction amplitude. The antral response was abolished by bilateral section of the cervical vagus nerves in five of six experiments. Selective extrinsic neurotomy of either compartment abolished all responses. It was concluded that the neural mechanisms controlling abomasal motility in the sheep resemble those found in species with simple stomachs: excitation of in-series tension receptors of the abomasal body causes an increase in antral contraction amplitude by vago-vagal reflex pathways. Antral motility is also modulated by changes of tension in the abomasal body by intrinsic reflex pathways and reflexes involving abdominal preganglia may also be present. In a restricted number of experiments the splanchnic nerve was shown to play an important role.     

A critical reticular site involved in the spino-bulbo-spinal reflex system

1. In precollicular decerebrate cats, the nucleus reticularis gigantocellularis in the medullar was identified to be critically involved in the spino-bulbo-spinal (SBS) reflex system. 2. Electrolytic lesion place in this nucleus eliminated the SBS reflex and its associated effects in the spinal cord. 3. Ascending volleys from the spinal cord were found to excite neurons within this nucleus, whereupon further direct stimulation was able to enhance the inhibitory effects of the SBS reflex on spinal motoneurons. These interactions were also facilitated by physostigmine and suppressed by atropine, indicating the cholinoceptive nature of these neurons, another criterion which qualified them as being associated with the SBS reflex. 4. The functional roles of SBS reflex and nucleus reticularis gigantocellularis in somatic and visceral activities were discussed.     

Participation of Ia reciprocal inhibitory neurons in the spinal circuitry of the tonic neck reflex

Summary As part of our studies of the spinal circuitry of the tonic neck reflex, we have recorded extracellularly from Ia reciprocal inhibitory neurons of the decerebrate, labyrinthectomized cat. The activity of a majority of neurons driven by stimulation of the quadriceps nerve was modulated by sinusoidal rotation of the neck; such modulation was much less frequent in the case of neurons driven by stimulation of nerves to more distal muscles. The results suggest that some of the inhibition which is part of the tonic neck reflex is mediated by Ia reciprocal inhibitory neurons, but that other pathways must also play an important role.     

The Notch locus and the genetic circuitry involved in early Drosophila neurogenesis

The genetic and molecular analysis of the Notch locus, which codes for a transmembrane protein sharing homology with the mammalian epidermal growth factor, suggests that the Notch protein is involved in a cell interaction mechanism essential for the differentiation of the embryonic nervous system of Drosophila. Taking advantage of the negative complementation between two Notch mutations that affect the extracellular domain of the protein, we have tried to dissect the genetic circuitry in which Notch is integrated by searching for genes whose products may interact with the Notch protein. This genetic screen has led to the identification of a surprisingly restricted set of interacting loci, including Delta and mastermind. Like Notch, both of these genes belong to a group of loci, the neurogenic loci, which have been previously identified by virtue of their similar mutant phenotype affecting early neurogenesis. We extend these studies by systematically exploring interactions between specific mutations in the Notch molecule and the other neurogenic genes. Furthermore, we show that the molecular lesions of two Notch alleles (nd and nd2), which interact dramatically with mastermind mutations, as well as with a mutation affecting the transducin homologous product of the neurogenic locus Enhancer of split, involve changes in the intracellular domain of the protein.     

The role of neuronal energy in the neurotoxicity of excitatory amino acids

Excitatory amino acids, acting at receptors such as the N-methyl-D-aspartate (NMDA) subtype, are good candidates for a major role in the neuronal death characteristic of Alzheimer's disease. Recent evidence from studies with cultured neurons suggests that perturbations in the energy metabolism of the neuron may be involved in the transition of NMDA agonists from neurotransmitters to neurotoxins via a mechanism that involves relief of the voltage-dependent Mg++ block of the NMDA channel.     

神经生长因子通路调节大鼠结肠的肠神经系统可塑性

目的探讨神经生长因子（NGF）是否可以诱导新生期母婴分离（NMS）模型下的肠神经系统（ENS）可塑性。方法雄性SD大鼠出生后行NMS。每天NMS前10min腹腔注射K252a（非特异性神经生长因子受体TrK拮抗剂）阻断NGF信号,对正常新生鼠每天注射NGF模拟NMS诱导的肠神经可塑性。8周后腹壁撤退反射检测内脏痛觉过敏。通过铺片技术和免疫荧光技术。比较各组近端结肠神经节（HuD阳性细胞）大小和数目以及胶质细胞的变化。检测肌间神经丛和粘膜下神经丛肠神经递质类型（ChAT,VIP,nNOS,Cab,TrKA,P75阳性细胞）,分析神经递质的可塑性变化。结果新生期应激可致成年鼠内脏敏感性增高,NGF可诱导内脏敏感性增高,K252a能使之部分缓解。NGF可以诱导部分神经结构重排、近端肌间神经丛ChAT的增高,所有结果经统计学分析,差异有统计学意义。结论早期生活事件是引起成年后肠神经系统可塑性改变的重要原因。这种可塑性变化可能是依赖NGF通路调节。     

Notch signal organizes the Drosophila olfactory circuitry by diversifying the sensory neuronal lineages

An essential feature of the organization and function of the vertebrate and insect olfactory systems is the generation of a variety of olfactory receptor neurons (ORNs) that have different specificities in regard to both odorant receptor expression and axonal targeting. Yet the underlying mechanisms that generate this neuronal diversity remain elusive. Here we demonstrate that the Notch signal is involved in the diversification of ORNs in Drosophila melanogaster. A systematic clonal analysis showed that a cluster of ORNs housed in each sensillum were differentiated into two classes, depending on the level of Notch activity in their sibling precursors. Notably, ORNs of different classes segregated their axonal projections into distinct domains in the antennal lobes. In addition, both the odorant receptor expression and the axonal targeting of ORNs were specified according to their Notch-mediated identities. Thus, Notch signaling contributes to the diversification of ORNs, thereby regulating multiple developmental events that establish the olfactory map in Drosophila.     

A neuronal subpopulation in the mammalian enteric nervous system expresses TrkA and TrkC neurotrophin receptor-like proteins

Increasing evidence suggests that, in addition to peripheral sensory and sympathetic neurons, the enteric neurons are also under the control of neurotrophins. Recently, neurotrophin receptors have been detected in the developing and adult mammalian enteric nervous system (ENS). Nevertheless, it remains to be established whether neurotrophin receptors are expressed in all enteric neurons and/or in glial cells and whether expression is a common feature in the enteric nervous system of all mammals or if interspecific differences exist. Rabbit polyclonal antibodies against Trk proteins (regarded as essential constituents of the high-affinity signal-transducing neurotrophin receptors) and p75 protein (considered as a low-affinity pan-neurotrophin receptor) were used to investigate the cell localization of these proteins in the ENS of adult man, horse, cow, sheep, pig, rabbit, and rat. Moreover, the percentage of neurons displaying immunoreactivity (IR) for each neurotrophin receptor protein was determined. TrkA-like IR and TrkC-like IR were observed in a neuronal subpopulation in both the myenteric and submucous plexuses, from esophagus to rectum in humans, and in the jejunum-ileum of the other species. Many neurons, and apparently all glial cells, in the human and rat enteric nervous system also displayed p75 IR. TrkB-like IR was found restricted to the glial cells of all species studied, with the exception of humans, in whom IR was mainly in glial cells and a small percentage of enteric neurons (about 5%). These findings indicate that the ENS of adult mammals express neuronal TrkA and TrkC, glial TrkB, and neuronal-glial p75, this pattern of distribution being similar in all examined species. Thus, influence of specific neurotrophins on their cognate receptors may be considered in the physiology and/or pathology of the adult ENS. Anat. Rec. 251:360–370, 1998. © 1998 Wiley-Liss, Inc.     

Methylmercuric chloride induces activation of neuronal stress circuitry and alters exploratory behavior in the mouse

Methylmercury (MeHg) is a well-known neurotoxicant, responsible for neurological and cognitive alterations. However, there is very little information available on the effects of MeHg administration on activation of murine neuronal pathways involved in the stress response, and whether this is altered as a function of repeated exposure to MeHg. Moreover, interactions between MeHg and other psychogenic and inflammatory stressors have yet to be fully determined. Acute i.p. exposure of male C57BL/6J mice to MeHg (2-8 mg/kg) dose-dependently attenuated exploratory behavior in the open field in the presence and absence of a novel object. In addition, increased numbers of c-Fos immunoreactive cells appeared in response to acute i.p. and i.c.v. MeHg within thalamic (anterior paraventricular nucleus of the thalamus (PVA)/posterior paraventricular nucleus of the thalamus (PV)), hypothalamic (paraventricular nucleus of the hypothalamus (PVN)), central amygdaloid nucleus (CeC), septal and hippocampal (dentate gyrus) nuclei, medial bed nucleus (BSTm) and the locus coeruleus (Lc). The increase in c-Fos positive cells in response to acute i.p. and i.c.v. MeHg did not appear to be influenced further by open field exposure. Repeated administration of MeHg led to an attenuation of most parameters of open field behavior altered by acute MeHg. However, increased c-Fos was significant in the CeC, Dg, supracapsular bed nucleus (BSTs), and Lc. Moreover, open field exposure after repeated treatments resulted in significant c-Fos responses in similar areas. Interestingly, 3 days after the final repeated MeHg dose (2 or 4 mg/kg) c-Fos increases to an immunogenic stressor (LPS) were not affected by MeHg pretreatment. These results demonstrate that systemic exposure to acute and repeated MeHg serves to activate the brain's stress circuitry, and furthermore appears to engage normal neuronal habituation processes.