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Basal ganglia volumetric studies in affective disorder: what did we learn in the last 15 years?

Until today, morphometric neuroimaging studies on affective disorders concentrate on the limbic system, especially the hippocampus, amygdala, and anterior cingulate. In most of the studies and reviews available today, the basal ganglia are of secondary interest. It seems that the basal ganglia are interest of neurologist, whereas the limbic system is reserved for psychiatric neuroimaging studies. We follow a different approach in this review, studying all available papers on MRI research of the basal ganglia in unipolar depression and bipolar disorder. We found a possibly larger neostriatum in bipolar and possibly smaller one in unipolar patients. None of the unipolar studies found any larger basal ganglion, and only one out of 12 bipolar studies found smaller basal ganglia. Both findings seemed to depend on age (tendency toward smaller volumes in unipolar and bipolar with older age), sex (men tending to pathology in both disorders) and bipolar patients show a possible influence of medication, which is not assessed so far in unipolar depression. We conclude that several methodological shortcomings in volumetric MRI research on the basal ganglia in affective disorders make it necessary to imply more research in this area. We suggest (a) better MRI methods (we do not have a single volumetric 3 Tesla study in this patient group); (b) studies of medication-naïve patients (thus ruling out the medication effect); (c) Studies that directly compare unipolar depressed and bipolar patients are needed to determine whether these apparent differences in morphometric abnormalities, as observed through the mediating comparison with healthy subjects, are real.

Basal Ganglia↗

Selective facilitatory effect of vasoactive intestinal polypeptide (VIP) on muscarinic firing in vesical ganglia of the cat.

VIP immunoreactivity was identified in nerve fibers and in 10-13% of the neurons in pelvic and bladder ganglia of the cat. Ninety percent of the VIP positive neurons contained acetylcholinesterase. VIP immunoreactivity was not altered in decentralized ganglia 1 week to 8 months after transection of the pelvic and hypogastric nerves indicating that VIP fibers arose from neurons within the peripheral nervous system. The intra-arterial administration of VIP (1-50 micrograms/kg) enhanced the postganglionic discharge elicited by the muscarinic agonist, acetyl-beta-methylcholine, but did not alter the postganglionic firing elicited by the nicotinic agonist, tetramethylammonium or by electrical stimulation of preganglionic axons in the pelvic nerve. VIP did not elicit a postganglionic discharge in untreated ganglia, but did evoke a prolonged discharge in ganglia treated with an irreversible anticholinesterase agent, 217AO. This discharge was not affected by hexamethonium but was blocked by atropine. VIP suppressed the muscarinic inhibition of ganglionic transmission produced by acetyl-beta-methylcholine without altering the response to other inhibitory agents (norepinephrine, leucine-enkephalin and gamma-aminobutyric acid (GABA). VIP (0.1-0.3 micrograms/kg) also had a direct inhibitory effect on bladder smooth muscle. These findings raise the possibility that intraganglionic pathways containing VIP may exert a selective modulatory influence on muscarinic transmission in vesical parasympathetic ganglia.

Acetylcholine↗

Axotomy alters putative neurotransmitters in visceral sensory neurons of the nodose and petrosal ganglia.

Acute peripheral axotomy of the visceral sensory neurons of the vagus and glossopharyngeal nerves removes peripheral depolarizing and trophic influences to their sensory ganglia. To study axotomy-induced changes in the putative neurotransmitters of visceral sensory neurons, rats were sacrificed 1, 3, 7 or 14 days after transection of either the cervical vagus and superior laryngeal nerves (to affect peripheral axotomy of the nodose ganglion) or the glossopharyngeal and carotid sinus nerves (to affect peripheral axotomy of the petrosal ganglion). The numbers of tyrosine hydroxylase (TH)-immunoreactive (ir), vasoactive intestinal peptide (VIP)-ir, calcitonin-gene-related peptide (CGRP)-ir, and substance P (SP)-ir neurons in the respective ganglia were analyzed in axotomized and control ganglia. In the nodose ganglion, axotomy of the cervical vagus resulted in a rapid (by 1 day) reduction in the number of TH-ir cells, whereas VIP-ir neurons were dramatically increased in number by 3 days. CGRP- and SP-ir cells in the nodose ganglion were relatively unaffected by axotomy. In the petrosal ganglion, axotomy of the glossopharyngeal and carotid sinus nerves greatly reduced the number of TH-ir cells but did not alter the number VIP-ir neurons. CGRP- and SP-ir neurons in the petrosal ganglion were reduced in number by axotomy. Thus, axotomy of visceral sensory neurons differentially changed the content and perhaps the expression of putative transmitters. Differential changes were seen among transmitters in a single ganglia and between ganglia. These data demonstrate the plasticity of putative neurotransmitter systems in visceral afferent systems of adult rats.

Animals↗

Age-related changes in the synaptic plasticity of rat superior cervical ganglia.

A few seconds of tetanic preganglionic stimulation of rat sympathetic ganglia results in potentiation of cholinergic synaptic transmission lasting several hours. However, ganglia from aged (28-32 months) rats did not develop as much potentiation as did ganglia from young (3-6 months) rats. This potentiation appears to decay exponentially but in two phases. The early component decays in 15 minutes, a time course consistent with the phenomenon of post-tetanic potentiation (PTP). The later component decays over several hours and is a form of long-term potentiation (LTP). A double exponential decay model was employed to quantitatively resolve the decay of potentiation and allow quantitative comparison of the decay parameters in both aged and young rats. It is clear that the magnitude and duration of PTP was the same in both age groups. However both the magnitude and decay time-constant for LTP were 30-50% smaller in the aged group of rats. Several agents which mimic cyclic AMP or stimulate cyclic AMP production in the ganglion enhance nicotinic transmission for several hours. However, these agents, 8-bromo cAMP, forskolin, isoproterenol, and secretin were equally effective in potentiating transmission in ganglia from both young and aged rats. Previous studies demonstrated that stimulus induced LTP and cyclic AMP induced potentiation was the result of enhanced release of acetylcholine (ACh) and not from increased postsynaptic responsiveness. Presumably these agents act through the same pathway and by the same mechanism that generates LTP following preganglionic tetany. These observations demonstrate that there is a selective age-dependent decline in the capacity for sympathetic ganglia to generate long-term changes in synaptic efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Release of neurite outgrowth promoting factors by Helisoma central ganglia depends on neural activity.

Identified buccal neurons B5 and B19 from the mollusc, Helisoma trivolvis, were plated into cell culture in order to assay for neurite outgrowth promoting factors released from central ring ganglia. The release and attachment of neurite promoting factors to the substratum of poly-lysine coated dishes could be inhibited by blocking spontaneous bioelectric activity in central ring ganglia used to condition the medium and dishes. Bioelectric activity within neurons in central ring ganglia was assayed by intracellular recording and found to be inhibited by exposure to the sodium channel blocker, tetrodotoxin (TTX; 2 x 10(-5) M), or CoCl2 (10 mM). Neither of these agents appeared to be toxic over a three day period since activity within neurons in central ring ganglia was restored following superfusion with saline. To examine the effect of blocking neural activity on the ability of central ring ganglia to release neurite outgrowth promoting factors, we compared the percentage of neurons that extended processes under 5 different conditions: (1) dishes containing conditioned medium and substrate attached growth factors (Super SAM); (2) dishes with substrate attached growth factors only and defined medium (SAM); (3) dishes containing substrate attached growth factors prepared in the presence of TTX; or (4) CoCl2; and (5) dishes containing unconditioned defined medium. The percentage of neurons extending processes under the 5 conditions were: (1) 71% (n = 32); (2) 51% (n = 33); (3) 14% (n = 37); (4) 15% (n = 47); (5) 0% (n = 40), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Selective alterations in transglutaminase activity of rat superior cervical ganglia in response to neurotransmitters, high potassium and sialic acid-containing compounds.

We examined the in vitro effects of neurotransmitters, high KCl as well as sialic acid-containing compounds (GM1; SC) on transglutaminase (TG) activity in isolated superior cervical ganglia (SCG) one week after denervation or axotomy. Following denervation, TG activity in SCG decreased to 83% of the unoperated control value, whereas that of axotomized ganglia was 28% of control. Thus, TG activity was relatively unaffected when sympathetic ganglionic neurons were preserved, but was markedly reduced under conditions where neurons were degenerating. Addition of ACh (0.1 mM) to the medium during aerobic incubation stimulated TG activity more than 3-fold in denervated ganglia but had no effect on TG activity in axotomized ganglia. Similarly, the NE (0.05 mM)-induced decrease of TG activity observed in intact SCG was also seen following denervation (-49%) but not following axotomy. In denervated SCG, the stimulatory effects of ACh were virtually abolished by co-addition of the cholinergic antagonists, atropine or hexamethonium, while the suppressant effects of NE were blocked by the adrenergic antagonists, propranolol, prazosin or yohimbine. These results imply that transmitter-induced rapid changes in TG activity occur predominantly in ganglionic neurons. When the ganglia were depolarized by high KCl (50 mM), a significant increase in TG activity in each intact, denervated and axotomized SCG was seen with qualitatively similar manner, suggesting that high KCl-induced depolarization affects both neuronal and glial components in the SCG. The marked increase in ganglionic TG activity in response to GM1 (5 nM) and synthetic SC (0.02 mM) were lost in denervated SCG but only partially reduced in axotomized SCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Comparison of the distributions of renal and splenic neurons in sympathetic ganglia.

Postganglionic neurons in different sympathetic ganglia are innervated selectively by preganglionic neurons originating from different segments of the spinal cord. These selective connections between pre- and postganglionic neurons may determine the specificity with which postganglionic nerves participate in differential reflex reactions. Because specificity of renal and splenic nerve responses to stimulation of visceral afferent nerves may depend on the distribution of postganglionic neurons in sympathetic ganglia, retrograde axonal transport of horseradish peroxidase was employed in this study to identify the ganglionic distribution of cell bodies of postganglionic neurons supplying the kidney and spleen in cats. Superior mesenteric, left and right celiac ganglia usually are fused together into a complex ganglion (solar plexus) in the cat. Most labeled cell bodies of renal nerves were clustered in groups within the solar plexus, but some cell bodies of renal neurons were observed in upper lumbar (L1-L3) and lower thoracic (T12-T13) paravertebral sympathetic ganglia. In contrast, 90% of labeled splenic neurons were scattered randomly throughout the left and right celiac poles of the solar plexus. In conclusion, the disparate distribution of renal and splenic neurons in sympathetic ganglia provides an anatomical basis for differential reflex responses in the two populations of nerves.

Animals↗

Parasympathetic ganglia innervating the canine atrioventricular nodal region.

Surgical disruption of the small (approximately 0.7 x 1.0 cm) epicardial fat pad situated at the junction of the inferior vena cava (IVC) and inferior surface of the left atrium (ILA) interrupts both right and left vagal input to the atrioventricular nodal (AVN) region of the canine heart. This intervention eliminates AV block during supramaximal stimulation of both cervical vagi, without interfering with sinus bradycardia normally associated with sinoatrial nodal (SAN) suppression. Independent modulation of SAN and AVN activities by the parasympathetic system is thereby revealed. Histology of the excised IVC-ILA fat pad reveals multiple well organized autonomic ganglia. These ganglia range from 2 to 80 cells per cluster and are associated with numerous nerve trunks. Individual ganglia are commonly surrounded by fatty connective tissue closely adjacent to epicardial muscle. They have not been found imbedded within atrial muscle and have been been found in or close to endocardial muscle layers. Other ganglia, imbedded in the fat pad overlying the posterior surface of the left atrium or in the atrioventricular groove, do not directly modulate A-V conduction. Surgical dissection around the extreme left or middle segments of the great cardiac vein and the coronary sinus failed to interrupt either left or right vagal input to the AVN region. Parasympathetic, preganglionic pathways to these AVN synapses do not, therefore, course from left to right along the atrioventricular groove. However, dissection around the extreme right portion of the coronary sinus at its penetration of the inferior interatrial septum, did interrupt vagal influences upon A-V conduction. Thus, numerous autonomic ganglia have been localized in the canine heart which serve as synaptic stations mediating both right and left vagal regulation of A-V conduction.

Adipose Tissue↗

Immunohistochemical characterisation of viscerofugal neurons projecting to the inferior mesenteric and major pelvic ganglia in the male rat.

Viscerofugal neurons in the myenteric plexus project out of the gut to the sympathetic neurons of the prevertebral ganglia and form the afferent arm of the intestino-intestinal inhibitory reflexes. In this study, we retrogradely labelled viscerofugal neurons in the middle and distal colon, and rectum which project to or through the inferior mesenteric ganglion and major pelvic ganglia. We found that 57-81% of these neurons contained immunoreactivity to calbindin, 37-70% contained immunoreactivity to bombesin, and 22-37% contained immunoreactivity to nitric oxide synthase, irrespective of the ganglion to which they projected. However, only 0-12% of viscerofugal neurons labelled in the rectum from the inferior mesenteric ganglion or intermesenteric nerves contained immunoreactivity to vasoactive intestinal peptide (VIP). In contrast, about 45% of viscerofugal neurons labelled from the pelvic ganglia contained VIP. We also have utilised immunoreactivity to bombesin to demonstrate, for the first time, the presence of viscerofugal terminals surrounding some sympathetic neurons in the major pelvic ganglia. The enteric origin of these terminals was confirmed by their degeneration following severance of the connections between the pelvic ganglia and the lower bowel. Our observation that some pelvic neurons receive viscerofugal input suggests that they can integrate peripheral and central messages. However, the majority of pelvic neurons do not receive viscerofugal input and would be predicted simply to relay central messages.

Animals↗

Proenkephalin opioid peptide product in the sensory ganglia of the rat: a developmental immunohistochemical study.

The distribution and development of Met-enkephalin-Arg6-Gly7-Leu8 (Enk-8)-containing neurons in the sensory ganglia of the rat were investigated by means of immunocytochemistry using specific antiserum to this octapeptide. Enk-8-like immunoreactivity first appeared in neurons of the trigeminal ganglia of the 18-day embryo, then in the dorsal root ganglia of the 21-day embryo, thus exhibiting a rostrocaudal gradient in terms of appearance and abundance. The number of immunoreactive neurons in these sensory ganglia peaked on the 5th-7th postnatal days, with several small ones observed in each section (1.0-1.4% of total cell number). About 30-40% of these Enk-8-like immunoreactive neurons were also immunoreactive to substance P. Subsequently, Enk-8-like immunoreactivity in the sensory ganglia was decreased and was rarely detected in adult animals. However, colchicine treatment revealed the presence of several Enk-8-containing neurons per section prepared from mature rat. All these neurons were small (12.5-25 microns; mean +/- S.E.M., 19.86 +/- 3.26 microns). Some of these were also immunoreactive to substance P. These results strongly suggest that the preproenkephalin A system exists in subpopulations of both developing and matured sensory cells in the rat. Functional significance of this is discussed.

Aging↗

Role of basal ganglia in behavioral learning.

Recent studies on single neuron activity revealed that activities of many basal ganglia neurons are dependent upon the behavioral context. This may give us a reason why observed movement-related activity in the basal ganglia occurred late in relation to prime mover muscle activity. Early onset activity of primate putamen neurons was reported in a study in which animals were required to make a performance of sequential limb movements. This suggests the participation of basal ganglia in the initiation of movement in a behavioral context-dependent manner. The context-dependent activity in the basal ganglia has been shown to be acquired through learning. For instance, midbrain dopamine neurons respond to external sensory stimuli or reward only during early stages of learning motor tasks. Striate neurons acquire task-related activity through learning and the acquired activity almost disappears after selective lesions of nigrostriatal dopamine. In this article, a hypothetical scheme of basal ganglia functioning in behavioral learning is presented. Limbic input conveys information related to 'reinforcement' or 'incentive' either directly to the striatum or indirectly through nigrostriatal dopamine system, and it contributes to the acquisition and expression of learned activity in the striatum. The expression of learned striatal activity would contribute to the initiation of learned motor behavior.

Animals↗

Calcitonin gene-related peptide increases in the dorsal root ganglia of adjuvant arthritic rat.

We examined the effect of adjuvant arthritis on the content of immunoreactive calcitonin gene-related peptide (iCGRP) in the dorsal root ganglia at L4-L6 levels and the spinal cord at a lumbar level in rats. Arthritis was induced by inoculating adjuvant into both hind-paws twice at a 10 day interval. In the arthritic rats 15 days after the first inoculation (day 15), the content of iCGRP was significantly increased in the dorsal root ganglia, with no change in the dorsal and ventral horns. The content in the dorsal root ganglia was still high on day 26 and had decreased by day 40. An intrathecal injection of colchicine (0.2 mg, 18 hr before killing) enhanced the increase of iCGRP in the dorsal root ganglia and decreased it in the dorsal horn of arthritic rats, although in noninoculated rats such treatment produced no significant changes in the content of iCGRP in both regions. The arthritis-induced increase in the content of iCGRP in the dorsal root ganglia was significantly reduced after treatment with the antiinflammatory analgesic, diclofenac sodium, in a dose of 3 mg/kg/day, PO for 10 days. Swelling and hyperalgesia in the hind-paw were depressed after such treatment. These results suggest that adjuvant arthritis with long-lasting inflammation with pain facilitates the turnover, especially biosynthesis, of CGRP in primary afferent neurons.

Animals↗

The histopathology of fibrous flexor sheath ganglia.

In order to determine if fibrous flexor sheath ganglia had any histological features that could distinguish them from other ganglia, wer reviewed 50 consecutive ganglia treated by surgical excision. Of these, eight were fibrous flexor sheath ganglia. They did not have any specific features to distinguish them from the other ganglia. Furthermore, an absence of true synovial lining in them refutes the theory that they may result from synovial herniation around the A1 pulley.

Adolescent↗

Muscarinic cholinergic receptors in dorsal root ganglia of chick embryo: a radioligand binding and immunocytochemical study.

The presence and micro-anatomical localization of muscarinic cholinergic receptors were assessed in dorsal root ganglia of chick embryo during development using radioligand binding and immunocytochemical techniques, respectively. The non-selective muscarinic cholinergic receptor radioligand [3H]quinuclidinyl benzilate was specifically bound to sections of chick dorsal root ganglia with a dissociation constant value (Kd) of 0.75 +/- 0.02 nM and a maximum density of binding sites (Bmax) of 7.2 +/- 0.5 fmol/mg tissue. [3H]Quinuclidinyl benzilate binding was partially sensitive to pirenzepine displacement. This suggests that muscarinic cholinergic receptors expressed by dorsal root ganglia of chick embryo at least in part belong to the M1 muscarinic receptor subtype. Immunocytochemical analysis confirmed the presence of muscarinic receptors in the ganglia. These findings suggest that neurons of dorsal root ganglia, which are known to express cholinergic markers such as choline acetyltransferase, acetylcholinesterase and high affinity choline uptake, are also cholinoceptive.

Animals↗

Nitric oxide release and long term potentiation at synapses in autonomic ganglia.

1. Long-term potentiation (LTP) of synaptic transmission in autonomic ganglia is reviewed, together with the possible role of nitric oxide (NO) in this process. 2. Calcium levels in preganglionic nerve terminals are elevated during at least the induction phase of LTP following a tetanus as well as during LTP induced by transmitter substances acting on the nerve terminals. Of the large number of calcium-dependent processes in the nerve terminal that might affect transmitter release, only calcium-calmodulin has been shown to be important in both the induction and maintenance of LTP. 3. The possibility that there is a decrease in the open time of nerve-terminal potassium channels following a tetanus, leading to an increase in duration of the terminal action potential and hence an increase in calcium influx and transmitter release is considered. There is little evidence for such an effect as yet for preganglionic nerve terminals. 4. Phosphorylation of potassium channels by cAMP-dependent protein kinase can lead to their inactivation with consequent action potential broadening in some systems. Exogenous cAMP enhances synaptic efficacy at preganglionic nerve terminals. Whether this occurs through an inactivation of potassium channels is not known. 5. Nitric oxide (NO) synthase is present in both sympathetic ganglia and the ciliary ganglia. NO increases synaptic efficacy in both ganglia. In at least the case of ciliary ganglion this is due to elevation of quantal secretion. 6. NO can in some conditions increase the terminal action potential duration in ciliary ganglia, probably through decrease in the Ic potassium current. There is evidence that this happens through cGMP modulating cAMP phosphodiesterases, thereby affecting cAMP phosphorylation of the Ic channel. 7. Blocking NO synthase markedly decreases LTP following a tetanus in the ciliary ganglion. The possibility is considered that NO is released from the terminal during a tetanus and through altering cAMP phosphorylation of Ic enhances transmitter release.

Animals↗

Auditory cortical field projections to the basal ganglia of the cat.

Projections to the basal ganglia from four auditory cortical fields in the cat were studied by combining microelectrode-mapping of the neurons' best frequencies with autoradiographic and histochemical tract-tracing techniques. Each auditory field is a source of projections to the homolateral basal ganglia. The distribution of labeling within the basal ganglia is related to the cortical field in which the injection site is located. The dorsal portion of the putamen and adjacent caudate nucleus are connected with cortical fields situated anteriorly and dorsally, while the ventral portion of the putamen and adjacent lateral amygdaloid nucleus are related to auditory fields situated posteriorly and ventrally. Injections of two different tracers into different best-frequency loci of one cortical field provided evidence that low best-frequency neurons project medially within the basal ganglia while high best-frequency neurons project more laterally. We concluded that there was a basic similarity among patterns of terminations in the basal ganglia from axons that originate in different auditory cortical fields. When the source of a projection was confined to a restricted portion of an auditory cortical field, labeling appeared as dense patches of silver grains separated from each other by areas of less dense labeling. Often, these patches were distributed within a sheet of tissue, elongated both dorsoventrally and anteroposteriorly. Loci having the same best-frequency representation, but situated in different auditory cortical fields, project upon overlapping but not coextensive portions of a single sheet of tissue. Thus the projections from geographically distant cortical loci possessing similar best-frequency representations are notably distinguished on a topographic basis. By comparison, two adjacent sheets of tissue were labeled when two injections were made into the low best-frequency and high best-frequency representations of the same auditory field. Double-injection, double-tracer experiments revealed that adjacent sheets of tissue received projections from different best-frequency loci. These observations suggested a degree of tonotopic organization to this projection system which was equipoise to the evidence obtained for a topographic organization.

Animals↗

Atrial natriuretic factor in sympathetic ganglia of the rat: dependence on cholinergic innervation.

Atrial natriuretic factor is detectable in the peripheral autonomic ganglia of the rat by radioimmunoassay and immunohistochemistry. In the present study, surgical and neurochemical methods were used to evaluate the source of this peptide in sympathetic ganglia. Decentralization of the ganglia and/or central administration of colchicine diminished the atrial natriuretic factor content in para- and prevertebral ganglia. Axotomy did not affect levels of ganglionic atrial natriuretic factor. A messenger ribonucleic acid species hybridizing with rat atrial natriuretic factor complementary deoxyribonucleic acid was not found within the total ribonucleic acid extracted from superior cervical ganglia. These results indicate a direct dependence of ganglionic atrial natriuretic factor on cholinergic innervation.

Acetylcholine↗

Distribution and morphological characterization of viscerofugal projections from the large intestine to the inferior mesenteric and pelvic ganglia of the male rat.

Viscerofugal neurons are enteric neurons in the myenteric plexus of the stomach and intestine that project to the prevertebral ganglia as the afferent limb of intestino-intestinal reflexes. This study characterizes viscerofugal projections to the inferior mesenteric ganglion and investigates the possibility of similar projections to the major pelvic ganglia in the male rat. The colon and rectum were examined for retrogradely labelled neurons following the injection of retrograde tracer into the inferior mesenteric or major pelvic ganglia, or following the application of tracer to the caudal end of the cut intermesenteric nerves, or either end of the cut hypogastric nerves. All labelled viscerofugal neurons were found in the myenteric plexus and were often grouped near the mesenteric attachment. The number of viscerofugal neurons projecting to the inferior mesenteric ganglion via the lumbar colonic nerves increases along the length of the large intestine with the maximum number of viscerofugal neurons found in the rectum. Some viscerofugal neurons from the distal colon and rectum reach the inferior mesenteric ganglion via the hypogastric nerves. A similar number and distribution of viscerofugal neurons project via the inferior mesenteric ganglion into the intermesenteric nerves as terminate in the inferior mesenteric ganglion. Very few viscerofugal neurons project to the neurons of the major pelvic ganglia via the rectal nerves, and no viscerofugal neurons project caudally in the hypogastric nerves to these ganglia. The majority of labelled neurons resembled Dogiel type I morphology. Thus the inferior mesenteric ganglion receives a substantial innervation from viscerofugal neurons of the large intestine, with the greatest supply from the distal colon and rectum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗