The digestive system is innervated through its connections with the central nervous system (CNS) and by the enteric nervous system (ENS) within the wall of the gastrointestinal tract. The ENS works in concert with CNS reflex and command centers and with neural pathways that pass through sympathetic ganglia to control digestive function. There is bidirectional information flow between the ENS and CNS and between the ENS and sympathetic prevertebral ganglia.The ENS in human contains 200-600 million neurons, distributed in many thousands of small ganglia, the great majority of which are found in two plexuses, the myenteric and submucosal plexuses. The myenteric plexus forms a continuous network that extends from the upper esophagus to the internal anal sphincter. Submucosal ganglia and connecting fiber bundles form plexuses in the small and large intestines, but not in the stomach and esophagus. The connections between the ENS and CNS are carried by the vagus and pelvic nerves and sympathetic pathways. Neurons also project from the ENS to prevertebral ganglia, the gallbladder, pancreas and trachea.The relative roles of the ENS and CNS differ considerably along the digestive tract. Movements of the striated muscle esophagus are determined by neural pattern generators in the CNS. Likewise the CNS has a major role in monitoring the state of the stomach and, in turn, controlling its contractile activity and acid secretion, through vago-vagal reflexes. In contrast, the ENS in the small intestine and colon contains full reflex circuits, including sensory neurons, interneurons and several classes of motor neuron, through which muscle activity, transmucosal fluid fluxes, local blood flow and other functions are controlled. The CNS has control of defecation, via the defecation centers in the lumbosacral spinal cord. The importance of the ENS is emphasized by the life-threatening effects of some ENS neuropathies. By contrast, removal of vagal or sympathetic connections with the gastrointestinal tract has minor effects on GI function. Voluntary control of defecation is exerted through pelvic connections, but cutting these connections is not life-threatening and other functions are little affected.

The gastrointestinal tract presents the largest and most vulnerable surface to the outside world. Simultaneously, it must be accessible and permeable to nutrients and must defend against pathogens and potentially injurious chemicals. Integrated responses to these challenges require the gut to sense its environment, which it does through a range of detection systems for specific chemical entities, pathogenic organisms and their products (including toxins), as well as physicochemical properties of its contents. Sensory information is then communicated to four major effector systems: the enteroendocrine hormonal signalling system; the innervation of the gut, both intrinsic and extrinsic; the gut immune system; and the local tissue defence system. Extensive endocrine-neuro-immune-organ-defence interactions are demonstrable, but under-investigated. A major challenge is to develop a comprehensive understanding of the integrated responses of the gut to the sensory information it receives. A major therapeutic opportunity exists to develop agents that target the receptors facing the gut lumen.

The importance of early experiences for mental health across the lifespan is well recognized. In particular, there is a strong association between adverse caregiving experiences and mental illness. However, relative to studies assessing outcomes in adults, there are far fewer studies assessing the earlier emerging manifestations of caregiving adversity during development. This lack of developmental research limits an understanding of the mechanisms that link adversity with mental illness. Adoption of a developmental approach to research in this field will yield greater insights into the factors that tie adversity to poor emotion function across a lifespan. In this review, we focus on recent findings that have used a developmental approach in the examination of mental health and early adversity. These studies are notable in that, across numerous species, they converge on the idea that early adversity leads to accelerated maturation of emotion circuits in the brain and in the behaviors supported by these regions. We propose that these ‘stress acceleration’ effects are evidence of early system adaptation.

From killers to curers: Peptides from cone snail venoms are potential therapeutic agents for the treatment of neuropathic pain. Unfortunately, these peptides suffer from the disadvantage of short biological half‐lives and poor activity when taken orally. A new orally active conotoxin was developed to solve these problems.

does not interact with N-type calcium channels directly but inhibits them via a voltage-independent mechanism involving a PTX-sensitive, G-protein-coupled receptor. Preincubation with a variety of selective receptor antagonists demonstrated that only the GABA B receptor antagonists, [S-(R*,R*)][-3-[[1-(3,4-dichlorophenyl)ethyl]amino]-2-hydroxy propyl]([3,4]-cyclohexylmethyl) phosphinic acid hydrochloride (2S)-3[[(1S)- 1-(3,4-dichlorophenyl

Early experiences critically shape the structure and function of the brain. Perturbations in typical/species-expected early experiences are known to have profound neural effects, especially in regions important for emotional responding. Parental care is one species-expected stimulus that plays a fundamental role in the development of emotion neurocircuitry. Emerging evidence across species suggests that phasic variation in parental presence during the sensitive period of childhood affects the recruitment of emotional networks on a moment-to-moment basis. In addition, it appears that increasing independence from caregivers cues the termination of the sensitive period for environmental input into emotion network development. In this review, we examine how early parental care, the central nervous system, and behavior come together to form a 'neuroenvironmental loop,' contributing to the formation of stable emotion regulation circuits. To achieve this end, we focus on the interaction of parental care and the developing amygdala-medial prefrontal cortex (mPFC) network-that is at the core of human emotional functioning. Using this model, we discuss how individual or group variations in parental independence, across chronic and brief timescales, might contribute to neural and emotional phenotypes that have implications for long-term mental health.

Located within the tunica muscularis of the gastrointestinal (GI) tract are networks of cells known as interstitial cells of Cajal (ICC). ICC are critical for important basic functions of GI motility such as generation and propagation of slow-wave pacemaker activity and reception of regulatory inputs from the enteric nervous system. We have developed a novel procedure to identify and isolate individual ICC from freshly dispersed cell preparations of the murine small intestine and gastric fundus and to determine differential transcriptional expression We have compared the expression profiles of pacemaker ICC isolated from the murine small intestine (IC-MY) and ICC involved in neurotransmission from the gastric fundus (IC-IM). We have also compared expression profiles between ICC and smooth muscle cells (SMC) and between freshly isolated ICC and cultured ICC. Cultured ICC express smooth muscle myosin, whereas freshly dispersed ICC do not. All cell types express muscarinic receptor types M(2) and M(3), neurokinin receptors NK(1) and NK(3), and inhibitory receptor VIP-1, whereas only cultured ICC and SMC express VIP-2. Both cultured and freshly dispersed IC-IM and IC-MY express the soluble form of stem cell factor, whereas SMC from the gastric fundus express only the membrane-bound form.

Recent studies in rats have shown that extinction occurring early in life is resistant to relapse and may represent the erasure of fear memories. In the present study we examined the effects of early life stress on extinction in the developing rat, which could have important implications for the treatment of anxiety disorders in those who have experienced early life stress. In the present study, we used maternal-separation on postnatal days (P) 2-14 as an early life stressor. On P17, maternally separated and standard-reared animals were trained to fear a noise associated with a footshock. The fear of this noise was then extinguished (through repeated nonreinforced noise presentations) on P18. Animals were tested for contextually mediated, stress-mediated, and GABA-mediated fear relapse the day after extinction. We found that young animals exposed to maternal-separation were more likely to exhibit context- and stress-mediated relapse after extinction than standard-reared animals (Experiments 1 and 2). Further, unlike standard-reared animals, maternally separated rats exhibited a return of fear when the inhibitory neurotransmitter GABA was blocked at test (Experiment 3). These effects were not the result of maternal separation increasing rats' sensitivity to footshock (Experiment 5) and may in part be related to superior long-term memory for contexts in P17 maternally separated rats (Experiment 4). Taken together, these results suggest that early life adversity may prepare young animals to respond more cautiously toward fear signals in their environment.