C. Morgan

Bio: C. Morgan is an academic researcher from University of Pittsburgh. The author has contributed to research in topics: Spinal cord & Efferent. The author has an hindex of 17, co-authored 18 publications receiving 2532 citations. Previous affiliations of C. Morgan include Yale University & United States Department of Veterans Affairs.

Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine

Abstract: Electrophysiological and horseradish peroxidase (HRP) techniques have provided new insights into the organization of the sacral parasympathetic reflex pathways to the large intestine and urinary bladder. The innervation of the two organs arises from separate groups of sacral preganglionic cells: (1) a dorsal band of cells in laminae V and VI providing an input to the intestine; and (2) a lateral band of cells in lamina VII providing an input to the bladder. These two groups of cells were separated by an interband region containing tract cells and interneurons. Neurons in the interband region received a visceral afferent input and exhibited firing correlated with the activity of intestine and urinary bladder. It seems reasonable therefore to consider the interband region as a third component of the sacral parasympathetic nucleus. Anterograde transport of HRP revealed that visceral afferents from the intestine and bladder projected into the parasympathetic nucleus. Most of the projections were collaterals from afferent axons in Lissauer's tract that passed in lamina I laterally and medially around the dorsal horn. These afferent collaterals were located in close proximity to preganglionic perikarya and dendrites in laminae I, V and VI. The proximity of visceral afferents and efferents in the sacral cord probably reflects the existence of polysynaptic rather than monosynaptic connections since electrophysiological studies revealed that both the defecation and micturition reflexes occurred with very long central delays (45-70 msec). The reflex pathways mediating defecation and micturition in cats with an intact neuraxis were markedly different. Defecation was dependent upon a spinal reflex with unmyelinated (C-fiber) peripheral afferent and efferent limbs. On the other hand, micturition was mediated by a spinobulbospinal pathway with myelinated peripheral afferent (A-fiber) and efferent axons (B-fiber). Transection of the spinal cord at T12-L2 blocked the micturition reflex but only transiently depressed the defecation reflex. In chronic spinal cats the micturition reflex recovered 1-2 weeks after spinalization; however, in these animals bladder-to-bladder micturition reflexes were elicited by C-fiber rather than A-fiber afferents. The C-fiber afferent-evoked reflex was weak or undetectable in animals with an intact neuraxis. Transection of the spinal cord also changed the micturition reflex in neonatal kittens (age 5-28 days). In neonates with an intact neuraxis bladder-to-bladder reflexes occurred via a long latency spinobulbospinal pathway (325-430 msec). The long latency is attributable to the slow conduction velocity in immature unmyelinated peripheral and central axons. In chronic spinal kittens (3-7 days after spinalization) the long latency reflex was abolished and a shorter latency (90-150 msec) bladder reflex was unmasked. The emergence of this spinal pathway may reflect axonal sprouting and the formation of new reflex connections within the sacral parasympathetic nucleus.

The distribution of visceral primary afferents from the pelvic nerve to Lissauer's tract and the spinal gray matter and its relationship to the sacral parasympathetic nucleus

Abstract: The central distribution of visceral primary afferent fibers from the pelvic nerve of the cast and the relationship of these fibers to preganglionic neurons of the sacral parasympathetic neurons (SPN) have been studied. Horseradish peroxidase (HRP) applied to the cut pelvic nerve was detected ipsilaterally in preganglionic neurons and dorsal root ganglion cells (segments S1-S3), and in central afferent projections to Lissauer's tract (LT), the dorsal columns, the dorsolateral funiculus, and spinal gray matter. The afferent projections were strongest in the region of the SPN (S1-S3) but extended far beyond its limits (e.g., LT was labeled from L4 to Cx7). In the transverse plane, collateral fiber bundles formed a thin shell around the dorsal horn predominantly within lamina I and expanded into terminal fields in the gray matter. The more prominent lateral collateral projection (LCP) extended into laminae V and VI, whereas the medial one (MCP) ended in the dorsal commissure. In longitudinal planes these projections exhibited a periodicity with an interval of approximately 200 micrometer. The distribution of afferent collateral projections overlaps the regions where many preganglionic neurons and their dendritic extensions are located, and also areas known to contain interneurons involved in visceral pathways. A differential distribution of afferents within the SPN was noted where a higher intensity was observed in proximity to those neurons located in laminae V and VI, which innervate the colon, and a lower intensity near neurons located in Lamina VII which innervate the bladder. This is consistent with the known spinal control of colon reflexes and the supraspinal control of bladder reflexes. The widespread rostrocaudal extent of the pelvic primary afferent projection is consistent with the necessity for the integration of somatic and autonomic elements from various levels of the lumbo-sacral-coccygeal spinal cord in the performance of pelvic visceral functions.

Baseline startle amplitude and prepulse inhibition in Vietnam veterans with posttraumatic stress disorder.

Abstract: Although an exaggerated startle response is a symptom of posttraumatic stress disorder (PTSD), empirical support for elevated baseline startle in PTSD has been weak. The present study investigated the eyeblink component of the acoustic startle reflex and prepulse inhibition (PPI) in 21 unmedicated Vietnam veterans with PTSD and in 17 civilian and 10 combat veteran comparison subjects. Patients with PTSD exhibited normal acoustic startle amplitude, but showed a significant reduction in PPI relative to the civilian subjects. There was only a trend toward a reduction in PPI in the PTSD group compared with the combat control group. The study does not support the hypothesis of exaggerated baseline startle in Vietnam veterans with PTSD but suggests abnormal startle modulation by a prepulse (i.e., PPI). Discrepancies between studies concerning the amplitude of startle in PTSD are discussed.

Organization of afferent and efferent pathways in the pudendal nerve of the female cat.

Abstract: Application of horseradish peroxidase to the pudendal nerve in the female cat labelled lumbosacral afferent and efferent neurons and their processes. Afferent axons entered the spinal cord primarily at the S1 and S2 segments and traveled rostrocaudally in Lissauer's tract and the dorsal columns. A distinctive component of the dorsal column projection was located at the lamina I-dorsal column border as a densely labelled, compact bundle that distributed fibers to the dorsal horn at spinal levels near the segments of entry of the afferent axons. Afferent terminal labelling was located in the marginal zone, the intermediate gray matter, and the dorsal gray commissure in the lumbosacral and coccygeal spinal cord. A well-defined terminal field restricted to the S1 and rostral S2 segments was present in the medial third of the nucleus proprius and substantia gelatinosa. Labelled motoneurons in Onuf's nucleus (S1 and S2) exhibited longitudinal dendrites that extended rostrocaudally within the nucleus and three groups of transverse dendrites that emanated periodically from the nucleus and passed to the ventrolateral funiculus, the intermediate gray, and the dorsal gray commissure. Components of the pudendal nerve that innervate the anal and urethral sphincters were also labelled by injecting HRP into the respective sphincter muscles. Motoneurons innervating the anal and urethral sphincters were located in the dorsomedial and ventrolateral divisions, respectively, of Onuf's nucleus. Afferent projections from the two sphincters were similar; the most prominent terminations were present in the marginal zone, intermediate gray, and dorsal gray commissure. These results are discussed with respect to the physiological function of the pudendal nerve and its relationship with sacral autonomic pathways.

Location and morphology of parasympathetic preganglionic neurons in the sacral spinal cord of the cat revealed by retrograde axonal transport of horseradish peroxidase

Abstract: The distribution and morphology of preganglionic neurons in the sacral parasympathetic nucleus (SPN) of the cat have been studied with the horseradish peroxidase (HRP) tracing technique. HRP applied to the cut pelvic nerve was identified in cells located ipsilaterally, primarily in the intermediate gray matter. They formed a column approximately 10 mm long, usually contained within two, but occasionally three, sacral segments, S2 contained a majority of cells. In transverse sections the SPN had the appearance of an inverted "L". Cells were medium-sized, oval or spindle-shaped, and transversely oriented. They were distributed among two major components and one minor one: (1) dorsal band (34%) located mainly in lamina V beneath the dorsal horn (cells and dendrites horizontally oriented), (2) lateral band (64%) along the lateral edge of the gray matter in laminae VII through V (cells oriented dorsoventrally with dendrites extending within the nucleus and into the dorsolateral funiculus), and (3) a small group (2%) of cells at the rostral end of the SPN in lamina VII in the middle of the ventral horn. These data coupled with the results of other investigations indicate that the SPN has a viscerotopic organization wherein the colon is innervated primarily by cells in the dorsal band and the urinary bladder is innervated primarily by cells in the lateral band.

The amygdala modulates the consolidation of memories of emotionally arousing experiences

Abstract: Converging findings of animal and human studies provide compelling evidence that the amygdala is critically involved in enabling us to acquire and retain lasting memories of emotional experiences. This review focuses primarily on the findings of research investigating the role of the amygdala in modulating the consolidation of long-term memories. Considerable evidence from animal studies investigating the effects of posttraining systemic or intra-amygdala infusions of hormones and drugs, as well as selective lesions of specific amygdala nuclei, indicates that (a) the amygdala mediates the memory-modulating effects of adrenal stress hormones and several classes of neurotransmitters; (b) the effects are selectively mediated by the basolateral complex of the amygdala (BLA); (c) the influences involve interactions of several neuromodulatory systems within the BLA that converge in influencing noradrenergic and muscarinic cholinergic activation; (d) the BLA modulates memory consolidation via efferents to other brain regions, including the caudate nucleus, nucleus accumbens, and cortex; and (e) the BLA modulates the consolidation of memory of many different kinds of information. The findings of human brain imaging studies are consistent with those of animal studies in suggesting that activation of the amygdala influences the consolidation of long-term memory; the degree of activation of the amygdala by emotional arousal during encoding of emotionally arousing material (either pleasant or unpleasant) correlates highly with subsequent recall. The activation of neuromodulatory systems affecting the BLA and its projections to other brain regions involved in processing different kinds of information plays a key role in enabling emotionally significant experiences to be well remembered.

Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies.

Abstract: Rationale: Since the mid-1970s, cross-species translational studies of prepulse inhibition (PPI) have increased at an astounding pace as the value of this neurobiologically informative measure has been optimized. PPI occurs when a relatively weak sensory event (the prepulse) is presented 30–500 ms before a strong startle-inducing stimulus, and reduces the magnitude of the startle response. In humans, PPI occurs in a robust, predictable manner when the prepulse and startling stimuli occur in either the same or different modalities (acoustic, visual, or cutaneous). Objective: This review covers three areas of interest in human PPI studies. First, we review the normal influences on PPI related to the underlying construct of sensori- (prepulse) motor (startle reflex) gating. Second, we review PPI studies in psychopathological disorders that form a family of gating disorders. Third, we review the relatively limited but interesting and rapidly expanding literature on pharmacological influences on PPI in humans. Methods: All studies identified by a computerized literature search that addressed the three topics of this review were compiled and evaluated. The principal studies were summarized in appropriate tables. Results: The major influences on PPI as a measure of sensorimotor gating can be grouped into 11 domains. Most of these domains are similar across species, supporting the value of PPI studies in translational comparisons across species. The most prominent literature describing deficits in PPI in psychiatrically defined groups features schizophrenia-spectrum patients and their clinically unaffected relatives. These findings support the use of PPI as an endophenotype in genetic studies. Additional groups of psychopathologically disordered patients with neuropathology involving cortico-striato-pallido-pontine circuits exhibit poor gating of motor, sensory, or cognitive information and corresponding PPI deficits. These groups include patients with obsessive compulsive disorder, Tourette's syndrome, blepharospasm, temporal lobe epilepsy with psychosis, enuresis, and perhaps post-traumatic stress disorder (PTSD). Several pharmacological manipulations have been examined for their effects on PPI in healthy human subjects. In some cases, the alterations in PPI produced by these drugs in animals correspond to similar effects in humans. Specifically, dopamine agonists disrupt and nicotine increases PPI in at least some human studies. With some other compounds, however, the effects seen in humans appear to differ from those reported in animals. For example, the PPI-increasing effects of the glutamate antagonist ketamine and the serotonin releaser MDMA in humans are opposite to the PPI-disruptive effects of these compounds in rodents. Conclusions: Considerable evidence supports a high degree of homology between measures of PPI in rodents and humans, consistent with the use of PPI as a cross-species measure of sensorimotor gating. Multiple investigations of PPI using a variety of methods and parameters confirm that deficits in PPI are evident in schizophrenia-spectrum patients and in certain other disorders in which gating mechanisms are disturbed. In contrast to the extensive literature on clinical populations, much more work is required to clarify the degree of correspondence between pharmacological effects on PPI in healthy humans and those reported in animals.

Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review.

Abstract: Rationale: Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. Similar deficits in PPI are produced in rats by pharmacological or developmental manipulations. These experimentally induced PPI deficits in rats are clearly not animal models of schizophrenia per se, but appear to provide models of sensorimotor gating deficits in schizophrenia patients that have face, predictive, and construct validity. In rodents, disruptions in PPI of startle are produced by: stimulation of D2 dopamine (DA) receptors, produced by amphetamine or apomorphine; activation of serotonergic systems, produced by serotonin (5-HT) releasers or direct agonists at multiple serotonin receptors; and blockade of N-methyl-D-aspartate (NMDA) receptors, produced by drugs such as phencyclidine (PCP). Accordingly, dopaminergic, serotonergic, and glutamatergic models of disrupted PPI have evolved and have been applied to the identification of potential antipsychotic treatments. In addition, some developmental manipulations, such as isolation rearing, have provided non-pharmacological animal models of the PPI deficits seen in schizophrenia. Objective: This review summarizes and evaluates studies assessing the effects of systemic drug administrations on PPI in rats. Methods: Studies examining systemic drug effects on PPI in rats prior to January 15, 2001 were compiled and organized into six annotated appendices. Based on this catalog of studies, the specific advantages and disadvantages of each of the four main PPI models used in the study of antipsychotic drugs were critically evaluated. Results: Despite some notable inconsistencies, the literature provides strong support for significant disruptions in PPI in rats produced by DA agonists, 5-HT2 agonists, NMDA antagonists, and isolation rearing. Each of these models exhibits sensitivity to at least some antipsychotic medications. While the PPI model based on the effects of direct DA agonists is the most well-validated for the identification of known antipsychotics, the isolation rearing model also appears to be sensitive to both typical and atypical antipsychotics. The 5-HT PPI model is less generally sensitive to antipsychotic medications, but can provide insight into the contribution of serotonergic systems to the actions of newer antipsychotics that act upon multiple receptors. The deficits in PPI produced by NMDA antagonists appear to be more sensitive to clozapine-like atypical antipsychotics than to typical antipsychotics. Hence, despite some exceptions to this generalization, the NMDA PPI model might aid in the identification of novel or atypical antipsychotic medications. Conclusions: Studies of drug effects on PPI in rats have generated four distinctive models that have utility in the identification of antipsychotic medications. Because each of these models has specific advantages and disadvantages, the choice of model to be used depends upon the question being addressed. This review should help to guide such decisions.