Biomedical subjects

S E Loughlin

Publications and source records attributed to S E Loughlin.

At least 19 recordsLinked to original sources

PubMed2005

Regulation of Homer and group I metabotropic glutamate receptors by nicotine.

The present study focuses on the nicotine-induced modulation of mRNA and protein expression of a number of genes involved in glutamatergic synaptic transmission in rat brain over different time periods of exposure. A subchronic (3 days) but not the chronic (7 or 14 days) administration of nicotine resulted in the up-regulation of Homer2a/b mRNA in the amygdala while in the ventral tegmental area (VTA) no change in expression of either Homer2a/b or Homer1b/c was observed. Although the increase in Homer2a/b mRNA was not translated into the protein level in the amygdala, a slight but significant up-regulation of Homer1b/c protein was observed in the same region at day 3. Both Homer forms were up-regulated at the protein level in the VTA at day 3. In the nucleus accumbens, 14 days of nicotine treatment up-regulated mRNA of Homer2b/c by 68.2% (P < 0.05), while the short form Homer1a gene was down-regulated by 65.0% at day 3 (P < 0.05). In regard to other components of the glutamatergic signalling, we identified an acute and intermittent increase in the mRNA and protein levels of mGluR1 and mGluR5 in the amygdala. In the VTA, however, the effects of nicotine on mGluR mRNA expression were long-lasting but rather specific to mGluR1. Nevertheless, mGluR1 protein levels in the VTA area were up-regulated only at day 3, as in the amygdala. These data provide further evidence for the involvement of nicotine in the glutamatergic neuronal synaptic activity in vivo, suggesting a role for the newly identified Homer proteins in this paradigm.

Amygdala↗

PubMed1993

Ventral mesencephalic and cortical transplants into the rat striatum display enhanced activity for neutral endopeptidase 24.11 ('enkephalinase'; CALLA).

A role for neutral endopeptidase 24.11 (NEP) in growth and development is supported by the demonstration that NEP hydrolyses and inactivates a number of peptide growth factors including atrial natriuretic peptide, endothelins, bombesin-like peptides, and opioid peptides, including the enkephalins. In the present study, suspensions of cells obtained from the ventral mesencephalon or cortex of rat embryos (ED14) were implanted into the striatum of the adult rat brain. Three to 15 weeks after transplantation the relative distribution of NEP-positive cellular elements was visualized histochemically. NEP staining in the transplants consistently appeared before NEP staining in the surrounding host striatum supporting a relative increase in NEP activity in the transplants. The NEP staining richly visualized cells of varying size and morphology which lacked the normal organization of the host striatum. The histochemical staining in the transplants and the surrounding host tissue was completely blocked by a 100 nM concentration of the selective NEP inhibitors phosphoramidon or JHF-26, supporting the exclusive localization of NEP by this method. NEP localization in the embryonic (ED14) cortex and ventral mesencephalon was also confirmed, suggesting one possible origin for the NEP-positive cells visualized in the transplants. Fluorescent double-labeling studies for NEP and glial fibrillary acidic protein (GFAP) or transforming growth factor alpha precursor (TGF alpha p) revealed the presence of rich glial labeling within the transplants for both GFAP and TGFap. NEP-labeled cells in the transplants were closely associated with glial elements, however, only occasional glial elements in the transplants stained for NEP; supporting a non-astrocytic localization for the NEP in the transplants. The marked enhancement of NEP staining in the transplants may have significance for controlling the rate or pattern of growth of the transplanted cells through inactivation of peptide growth factors produced by, or in response to, the transplants.

Animals↗

PubMed1993

Long-term changes in striatal opioid systems after 6-hydroxydopamine lesion of rat substantia nigra.

The effects of unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway on striatal opioid peptides and receptors were determined at different time-intervals, from three days up to 24 weeks, post-lesion. Mu, delta and kappa opioid binding site densities in the ipsilateral caudate-putamen were decreased by 25-50% in rats which exhibited a greater than 90% loss of dopamine uptake sites. Differentiation of radioligand binding to kappa1 and kappa2 subtypes demonstrated a selective loss of kappa2 sites post-lesion. The onset of significant 6-hydroxydopamine lesion-induced changes in striatal opioid binding sites was delayed with respect to the loss of dopamine uptake sites. Furthermore, maximal loss of dopamine uptake sites was apparent within seven days post-lesion, but not until two to four weeks for mu, delta and kappa sites. In animals which exhibited an incomplete loss of dopamine uptake sites (less than 80%) there was no significant change in opioid binding site density. Striatal proenkephalin and prodynorphin messenger RNA levels were increased and decreased, respectively, after complete 6-hydroxydopamine lesion. Modulation of peptide messenger RNA levels was apparent within seven days and was maintained up to 24 weeks post-lesion. In contrast, proenkephalin and prodynorphin messenger RNA levels were unchanged in animals which exhibited an incomplete loss of striatal dopamine uptake sites. Taken together, these observations suggest that the majority of mu, delta and kappa2 opioid binding sites are localized on non-dopaminergic elements in the caudate-putamen, but that substantia nigra innervation plays a role in the control of striatal opioid receptor expression. The 6-hydroxydopamine lesion-induced decreases in striatal opioid binding site density may, in part, be a function of agonist-induced receptor downregulation. Alternatively, both opioid receptor and peptide expression in the caudate-putamen may be directly, but independently, regulated by ventral mesencephalic neurons.

Animals↗

PubMed1992

Opioid receptor changes in weaver mouse striatum.

The dopaminergic projection from the substantia nigra to the patch and matrix compartments of the caudate-putamen undergoes a spontaneous, early postnatal degeneration in mice which carry the weaver gene. The projection to nucleus accumbens is relatively spared. Dopaminergic afferents have been shown to be important modulators of striatal opioid receptor expression. In the present study, opioid receptor localization in the caudate-putamen and nucleus accumbens of control and weaver mice was examined by quantitative autoradiography. Mu, delta and kappa opioid receptors were differentially distributed in nucleus accumbens and in patch and matrix compartments of the caudate-putamen. In animals which were homozygous for the weaver gene, the density of mu opioid receptors in both patch and matrix compartments was unchanged with respect to control mice. In contrast, the density of delta and kappa opioid receptors was significantly decreased in weaver caudate-putamen and nucleus accumbens. The significance of these results with respect to opioid receptor expression and Parkinson's disease is discussed.

Animals↗

PubMed1992

Localization of acidic fibroblast growth factor within the mouse brain using biochemical and immunocytochemical techniques.

The localization of acidic fibroblast growth factor (aFGF) in the male mouse brain was studied with biochemical and immunocytochemical techniques. Using two peptide-based aFGF antisera directed against independent epitopes, Western gel analysis of dissected brain demonstrated significant levels of aFGF immunoreactivity in the pons-medulla, hypothalamus and cerebellum. The cortex contained much less immunoreactivity. Consistent with the biochemical data, immunocytochemical analysis with the same two antisera demonstrated that aFGF immunoreactivity is localized in neuronal cell bodies in these regions. Numerous immunoreactive neurons were observed in the reticular formation of the pons and medulla, as well as in several other brainstem nuclei and areas. Immunoreactive neurons were also present in the lateral and medial hypothalamus, and some thalamic, subthalamic and epithalamic nuclei. In the basal ganglia, immunoreactive neurons were present in the amygdala and septum. Few intensely stained immunoreactive neurons were observed in the striatum, pallidum and neocortex. Limbic cortices contained more numerous immunoreactive neurons than neocortex. These results support the concept that aFGF is present in the brain, where it is heterogeneously distributed in neuronal cell bodies in regions involved in sensory, extrapyramidal motor, limbic and autonomic functions. The results are consistent with various neurotrophic, mitogenic, and neuromodulatory functions associated with aFGF in the mammalian central nervous system.

Amino Acid Sequence↗

PubMed1992

kappa-Opioid inhibition of [3H]dopamine release from rat ventral mesencephalic dissociated cell cultures.

The present study investigated the effect of opioids on [3H]dopamine release from mixed neuronal-glial cell cultures of embryonic rat ventral mesencephalon. Each of the major morphological types of dopaminergic cell was represented in these cultures. These cells exhibited specific uptake of [3H]dopamine, which was subsequently released, in a calcium-dependent manner, in response to a double pulse of elevated extracellular potassium. Spontaneous and potassium-evoked [3H]dopamine release was inhibited by kappa- but not mu- or delta-opioid agonists. The selective kappa 1 agonist (5 alpha, 7 alpha, 8 beta)-(-)-N-methyl-N-[7-(1-pyrollidinyl)-1-oxaspiro(4,5)- dec-8-yl]benzeneacetamide (U69593) produced a dose-dependent inhibition of dopamine release. The effect of U69593 was blocked by the nonselective opiate antagonist naloxone and the selective kappa opioid antagonist norbinaltorphimine. kappa-Opioid inhibition of potassium-evoked [3H]dopamine release was maintained in the presence of tetrodotoxin. These results suggest that functional kappa receptors, modulating dopamine release, are localized on the terminals of dopaminergic neurons.

Animals↗

PubMed1991

Transient appearance of beta-endorphin immunoreactive cells within the germinal zone of neonatal rat forebrain.

Recent evidence implicates endogenous opioid systems in basic processes which underlie morphogenesis. The present report describes a population of cells within the germinal zone of the neonatal rat forebrain which are immunoreactive for the opioid peptide beta-endorphin and other peptides derived from the proopiomelanocortin precursor. These cells are present at the time of birth, but are no longer detectable by the sixth postnatal day. They have medially and laterally directed processes which extend to the ventricular wall and across the caudate putamen to its lateral border. Cells of similar morphology and distribution which are immunoreactive for two other proopiomelanocortin peptides, alpha-melanocyte stimulating hormone and adrenocorticotrophic hormone, were also observed in similar distributions during the same developmental period. These data are consistent with the hypothesis that cells within the germinal zone transiently synthesize proopiomelanocortin, which is further processed to yield these three peptide products. This finding may be important in understanding the role of proopiomelanocortin-derived peptides in neural development.

Adrenocorticotropic Hormone↗

PubMed1990

Natriuretic peptide receptors in cultured rat diencephalon.

To characterize the type of cell expressing natriuretic peptide receptors in the brain and the nature of these receptors, we conducted studies in primary cultured glial and neuronal cells derived from fetal rat diencephalon. The glial predominant cultures (95% of total cells and glial fibrillary acidic protein positive) expressed nearly a 10-fold greater specific binding of the natriuretic peptides to cell surface receptors compared with the neuron-predominant cultures. Scatchard analysis of binding studies with 125I-atrial natriuretic peptide (ANP) and 125I-brain natriuretic peptide (BNP) revealed a single class of receptors with dissimilar affinities (0.25 +/- 0.09 and 0.74 +/- 0.07 nM, respectively, n = 3 experiments p less than 0.01) but similar numbers of binding sites for both peptides (93 and 88 fmol/mg of protein, respectively). Cross-linking of 125I-ANP and BNP to cultured glia followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography identified distinct bands at either approximate Mr 130,000, or 102,000 and 66,000, corresponding to two high molecular weight (B) receptors and one low molecular weight (C) receptor described in other tissues. Different subtypes of astrocytes appeared to express different B receptors. Binding and cross-linking of radiolabeled ANP or BNP were competitively inhibited equally by unlabeled ANP or BNP, indicating that ANP and BNP probably bind the same receptors. The glial cultures functionally expressed a receptor(s) with guanylate cyclase activity; BNP was less potent than ANP in stimulating cGMP at lower concentrations. These results indicate that both high and low molecular weight natriuretic peptide receptors are expressed in astrocyte-predominant cultures from the fetal diencephalon and suggest that glia participate in several actions of ANP which are probably mediated through this area of the brain.

Animals↗

PubMed1990

Localization of cells containing transforming growth factor-alpha precursor immunoreactivity in the basal ganglia of the adult rat brain.

Transforming growth factor-alpha-like immunoreactivity (TGF-alpha-ir) was visualized in the adult rat forebrain using three antisera directed against carboxyterminal sequences in the TGF-alpha precursor. Using immunoperoxidase and immunofluorescence techniques with all three antisera, TGF-alpha-ir was found to be present in a subpopulation of astrocytes in the forebrain. Striatal and pallidal regions of the basal ganglia were studied in detail. In the striatum, there was an uneven distribution of astrocytes containing TGF-alpha-ir, with the greatest number in the dorsal medial third of the caudate-putamen and the overlying corpus callosum/external capsule. In addition, the region of the caudate-putamen bordering the globus pallidus contained numerous clusters of TGF-alpha-ir astrocytes. The globus pallidus itself contained numerous and more evenly distributed TGF-alpha-ir astrocytes. Other pallidal structures--including the ventral pallidum, entopeduncular nucleus, and substantia nigra pars reticulata--contained moderate numbers of TGF-alpha-ir astrocytes. These results suggest that TGF-alpha precursor is present and, perhaps, synthesized in astrocytes. A related growth factor, epidermal growth factor (EGF), has also been reported to be present in pallidal regions of rat brain. Therefore, the TGF-alpha/EGF family of trophic factors may play a role in the function of the central nervous system.

Animals↗

PubMed1987

Effects of morphine on DNA synthesis in neonatal rat brain.

Several observations have led to the hypothesis that endogenous opioids may modulate the growth and development of the brain. In the present study, we have examined the effect of morphine on the incorporation of [3H]thymidine into the DNA of neonatal rat brains in vivo and in vitro. We have found that morphine, when administered to one-day-old rats, inhibited [3H]thymidine incorporation into brain DNA in a long-lasting, naloxone-reversible manner. Morphine inhibited DNA synthesis in animals one and 4 days of age but not in older animals. This effect was tissue-specific, and did not appear to be due simply to respiratory depression or decreased availability of precursor to the brain. Naloxone, when administered acutely, or naltrexone, chronically, had no effect on [3H]thymidine incorporation, indicating that endogenous opioids do not tonically depress DNA synthesis. When neonatal brain tissue was incubated with morphine in vitro. [3H]thymidine incorporation values were not different from controls. These data indicate that the effect of morphine on DNA synthesis in vivo may be an indirect one, rather than a direct action on proliferating cells.

Animals↗

PubMed1987

Anatomical evidence for alpha-2 adrenoceptor heterogeneity: differential autoradiographic distributions of [3H]rauwolscine and [3H]idazoxan in rat brain.

Previous autoradiographic studies which have localized alpha-2 adrenoceptors within brain have used tritiated derivatives of clonidine and other alpha-2 adrenergic agonists. In the present study we have compared the autoradiographic distributions of binding sites labeled by two reportedly selective alpha-2 adrenoceptor antagonists, [3H]rauwolscine and [3H]idazoxan, in rat brain. The distribution of high affinity [3H]idazoxan binding sites differed markedly from that of high affinity [3H]rauwolscine sites throughout the neuraxis. The distribution of [3H]idazoxan binding sites paralleled closely that of [3H]clonidine sites, and corresponded to areas of noradrenergic innervation. Densest [3H]idazoxan labeling appeared over anterior olfactory nuclei, fundus striatum, septum, thalamus, hypothalamus, amygdala, entorhinal cortex, central gray, inferior colliculus, dorsal parabrachial nucleus, locus ceruleus and nucleus of the solitary tract. In contrast, much lower levels of [3H]rauwolscine labeling appeared over several areas which receive primarily dopaminergic innervation, and thus corresponded closely to [3H]spiroperidol binding distributions. Densest [3H]rauwolscine labeling appeared over nucleus caudate-putamen, nucleus accumbens, olfactory tubercle, Islands of Calleja, hippocampus, parasubiculum, basolateral amygdaloid nucleus and substantia nigra. In areas labeled by [3H]rauwolscine, computerized densitometric analysis of autoradiographic saturation curves revealed that the maximum binding values for [3H]idazoxan high affinity binding sites were consistently greater than those for high affinity [3H]rauwolscine sites. The pharmacological characterization of these two binding sites in the accompanying paper supports the present anatomical evidence that [3H]idazoxan labels a heterogenous population of alpha-2 adrenoceptor sites, one population of which is selectively labeled by [3H]rauwolscine.

Animals↗

PubMed1986

Efferent projections of nucleus locus coeruleus: topographic organization of cells of origin demonstrated by three-dimensional reconstruction.

The present study examines the spatial distribution within rat locus coeruleus of neurons projecting to particular brain regions. In order to accurately recreate, in digital and pictorial formats, the spatial distribution of neurons for the entire nucleus locus coeruleus, three-dimensional reconstructions were created which specified the location of each individual Nissl-stained locus coeruleus cell in each of five nuclei. Dynamic computerized displays were visually analyzed and statistically compared. The nuclei from different brains were found to be strikingly similar in density and distribution of cells. In order to determine whether the cells of origin for particular locus coeruleus projections were clustered within the nucleus, reconstructions were created of the distributions of cells labeled by injections of a retrograde tracer, horseradish peroxidase, into particular terminal regions. Groups consisting of animals with injections into the same target areas were visually and statistically compared. The cells of origin of most efferent projections were found to be spatially organized within locus coeruleus. Specifically, projections to both the dorsal and ventral hippocampus originated solely from the dorsal segment of the nucleus, while spinal cord projections originated from ventral-posterior locus coeruleus. Cells of origin of cerebral and cerebellar cortical efferents, as well as hypothalamic efferents, exhibited less clustering, although reliable differences in distribution were observed. The most striking example of clustered cells of origin was exhibited by the large norepinephrine-containing cells constituting the anterior pole of locus coeruleus which were labeled only by hypothalamic injections. This analysis of spatial organization within locus coeruleus is unique in its utilization of a defined control group, experimental groups consisting of strictly defined replications, accurate three-dimensional reconstruction, and statistical comparisons. The demonstrated spatial heterogeneity of locus coeruleus neurons with respect to efferent projections can now be compared to the spatial distributions of other cellular characteristics such as soma morphology, colocalized transmitters and physiological properties. Presumably, such spatial segregation reflects the operation of functionally important organizing principles within the nucleus.

Animals↗

PubMed1986

Efferent projections of nucleus locus coeruleus: morphologic subpopulations have different efferent targets.

This study quantitatively addresses the hypothesis that there is a systematic relationship between the morphologic characteristics of locus neurons and the particular target regions they innervate. Following horseradish peroxidase injections into selected terminal fields, locus coeruleus cell bodies are heavily labeled by retrograde transport so that somata size and shape, and in many cases primary dendritic pattern can be observed. This allows the classification of neurons as one of six cell types: large multipolar cells within ventral locus coeruleus, large multipolar cells in the anterior pole of locus coeruleus, fusiform cells in dorsal LC, posterior pole cells, medium-sized multipolar cells (termed core cells in this report), and small round cells. It was found that while core cells contribute to the innervation of all terminal fields examined, other cell types project to more restricted sets of targets. The contributions of each type to selected efferents are presented in detail. In particular, fusiform cells project to hippocampus and cortex, large multipolar cells in ventral locus coeruleus project to spinal cord and cerebellum, and small round cells in central and anterior locus coeruleus, as well as large multipolar cells in anterior locus coeruleus, project to hypothalamus. These results, in conjunction with those described in the preceding report, indicate that locus coeruleus is intrinsically organized with respect to efferent projections with much more specificity than has previously been evident. This high degree of organization is consistent with other recent demonstrations of functional specificity exhibited by locus coeruleus neurons.

Animals↗

PubMed1985

Noradrenergic changes and memory loss in aged mice.

The present paper addresses the question of whether a decline of central noradrenergic activity is associated with aging and memory loss in mice. Receptor binding techniques were utilized to compare alpha 2-adrenoceptor density in the brains of aged and young mice. Using [3H]rauwolscine, a selective alpha 2-adrenoceptor antagonist, two membrane binding sites were identified which were differentially affected by age. Whereas the density of high-affinity binding sites was unchanged in aged brain as compared to young controls, there was a significant decrease in the number of low-affinity sites. In a separate study, animals were tested for performance on a step-through inhibitory avoidance task, prior to sacrifice and morphological analysis of the brainstem noradrenergic nucleus locus coeruleus (LC). Aged mice exhibited a significant decrease in task retention as compared to young controls; a small, though non-significant, decline was also observed in the numbers of cells within LC. While young mice exhibited low within-group variance, individual aged animals differed greatly in both LC cell number and behavioral performance. Within the aged population, there was a highly significant correlation between the extent of LC cell loss and the degree of memory impairment. These results provide further evidence for an age-related decline in central noradrenergic function which may contribute to an associated memory loss.

Aging↗

PubMed1985

Few cortical cholecystokinin immunoreactive neurons have long projections.

Cholecystokinin (CCK)-like immunoreactive neurons have been reported to be widely distributed throughout both the neo- and allocortices. In the present study, we were interested in determining whether these cortical CCK neurons have long projections using the double-labeling technique of fluorescence retrograde tracing combined with immunofluorescence for CCK. The distribution of CCK immunoreactive perikarya and fibers was plotted throughout the rostro-caudal extent of the cerebral cortex in both untreated and colchicine-treated albino rats. In the double-labeling experiments, the animals received injections of fluorescent retrograde tracers into cortical, limbic, striatal or thalamic structures, followed one to two days later by colchicine treatment. Brains were subsequently processed for indirect immunofluorescence for CCK-octapeptide and fluorescent dye localization. It was found that 1) a small number of prefrontal cortical CCK neurons were double-labeled with both fluorescent dye and immunofluorescence for CCK after dye injection into midline thalamus, 2) only rarely were cortical CCK neurons double-labeled with injection of tracers into cortex, striatum, or other subcortical structures, 3) numerous midbrain CCK neurons were double-labeled after dye injection into prefrontal cortex and anterior cingulate cortex. and 4) colchicine or cannula injection damage to cortical forebrain tracts (corpus callosum, internal capsule, external capsule, anterior commissure) resulted in the appearance of numerous CCK immunoreactive fibers not normally seen in the undamaged tracts. Although the possibility remains that cortical CCK neurons may be refractory to transport of retrograde tracers, these results suggest that CCK-like immunoreactive neurons of the rat cerebral cortex are predominantly local circuit neurons and that only minor cortico-cortical and cortico-subcortical CCK-containing projections exist.

Animals↗

PubMed1985

Postnatal development of opioid systems in rat brain.

Immunocytochemical and receptor autoradiographic techniques have been utilized to examine the postnatal development of opioid peptides and receptors. The pattern of met-enkephalin-like immunoreactivity was very similar at birth to the adult, increasing only in intensity throughout postnatal development. In contrast, beta-endorphin-like immunoreactivity (BLI) in neonate was strikingly different from that of adult. In particular, cells and fibers were observed in germinal zones, structures present only in the neonate. The distribution of dynorphin-B-like immunoreactivity at birth was intermediate in its similarity to that of adult. Certain terminal fields were present, others developed postnatally, and others disappeared with age. In parallel studies, autoradiographic maps of mu, delta and kappa opioid receptor subtypes were generated to determine whether any correspondences existed between the developmental distribution of opioids and their receptors. Although significant overlap existed, no simple one-to-one relationship was observed. The differential localization of peptides and receptors in neonatal and adult brain suggests that opioids may subserve distinct functions in the neonate. In particular, the presence of BLI in the germinal zones, where postnatal neurogenesis occurs, implicates opioid systems in regulation of neuronal cell division.

Age Factors↗

PubMed1984

Epidermal growth factor immunoreactive material in the central nervous system: location and development.

Epidermal growth factor (EGF) is a potent mitogen with hormonal activity in the gastrointestinal tract. Material cross-reacting with EGF was detected in the central nervous system of the developing and adult albino rat by the indirect immunofluorescence technique. High concentrations of EGF-cross-reacting material were identified in forebrain and midbrain structures of pallidal areas of the brain. These include the globus pallidus, ventral pallidum, entopeduncular nucleus, substantia nigra pars reticulata, and the islands of Calleja . Thus, EGF may represent another gut-brain peptide with potential neurotransmitter-neuromodulator functions in pallidal structures of the extrapyramidal motor systems of the brain.

Animals↗

PubMed1984

Substantia nigra and ventral tegmental area projections to cortex: topography and collateralization.

The substantia nigra and ventral tegmental area of the rat were examined by retrograde transport methods to determine the topography and collateralization patterns of projections to cortex and certain subcortical sites. The topographical relationships between cells and their terminal fields were confirmed and clarified by the horseradish peroxidase retrograde transport technique. The collateralization of axons was analyzed by the use of multiple fluorescent tracers. These experiments indicated that individual ventral tegmental area cells do not collateralize extensively to either subcortical or cortical terminal fields. Substantia nigra cells, however, give rise to more highly collateralized axons and single cells may simultaneously innervate different regions of cortex as well as subcortical sites. Substantia nigra cells can be divided with respect to their cortical collateralization patterns into three groups: (1) those that innervate cingulate cortices, (2) those that project to prefrontal and suprarhinal cortices, and (3) those that innervate entorhinal cortex.

Afferent Pathways↗