ABSTRACT
Motion is a powerful cue for figure-ground segregation, allowing the recognition of shapes even if the luminance and texture characteristics of the stimulus and background are matched. In order to investigate the neural processes underlying early stages of the cue-invariant processing of form, we compared the responses of neurons in the striate cortex (V1) of anaesthetized marmosets to two types of moving stimuli: bars defined by differences in luminance, and bars defined solely by the coherent motion of random patterns that matched the texture and temporal modulation of the background. A population of form-cue-invariant (FCI) neurons was identified, which demonstrated similar tuning to the length of contours defined by first- and second-order cues. FCI neurons were relatively common in the supragranular layers (where they corresponded to 28% of the recorded units), but were absent from layer 4. Most had complex receptive fields, which were significantly larger than those of other V1 neurons. The majority of FCI neurons demonstrated end-inhibition in response to long first- and second-order bars, and were strongly direction selective. Thus, even at the level of V1 there are cells whose variations in response level appear to be determined by the shape and motion of the entire second-order object, rather than by its parts (i.e. the individual textural components). These results are compatible with the existence of an output channel from V1 to the ventral stream of extrastriate areas, which already encodes the basic building blocks of the image in an invariant manner.
Subject(s)
Callithrix/physiology , Motion Perception/physiology , Neurons/physiology , Pattern Recognition, Visual/physiology , Visual Cortex/physiology , Action Potentials/physiology , Animals , Callithrix/anatomy & histology , Cues , Lighting , Neural Inhibition/physiology , Photic Stimulation , Synaptic Transmission/physiology , Visual Cortex/cytology , Visual Pathways/cytology , Visual Pathways/physiologyABSTRACT
The extrastriate cortex near the dorsal midline has been described as part of an 'express' pathway that provides visual input to the premotor cortex. This pathway is considered important for the integration of sensory information about the visual field periphery and the skeletomotor system, especially in relation to the control of arm movements. However, a better understanding of the functional contributions of different parts of this complex has been hampered by the lack of data on the extent and boundaries of its constituent visual areas. Recent studies in macaques have provided the first detailed view of the topographical organization of this region in Old World monkeys. Despite differences in nomenclature, a comparison of the visuotopic organization, myeloarchitecture and connections of the relevant visual areas with those previously studied in New World monkeys reveals a remarkable degree of similarity and helps to clarify the subdivision of function between different areas of the dorsomedial complex. A caudal visual area, named DM or V6, appears to be important for the detection of coherent patterns of movement across wide regions of the visual field, such as those induced during self-motion. A rostral area, named M or V6A, is more directly involved with visuomotor integration. This area receives projections both from DM/V6 and from a separate motion analysis channel, centred on the middle temporal visual area (or V5), which detects the movement of objects in extrapersonal space. These results support the suggestion, made earlier on the basis of more fragmentary evidence, that the areas rostral to the second visual area in dorsal cortex are homologous in all simian primates. Moreover, they emphasize the importance of determining the anatomical organization of the cortex as a prerequisite for elucidating the function of different cortical areas.
Subject(s)
Cebidae/physiology , Cercopithecidae/physiology , Psychomotor Performance/physiology , Visual Cortex/physiology , AnimalsABSTRACT
In primates, lesions of striate cortex (V1) result in scotomas in which only rudimentary visual abilities remain. These aspects of vision that survive V1 lesions have been attributed to direct thalamic pathways to extrastriate areas, including the middle temporal area (MT). However, studies in New World monkeys and humans have questioned this interpretation, suggesting that remnants of V1 are responsible for both the activation of MT and residual vision. We studied the visual responses of neurons in area MT in New World marmoset monkeys in the weeks after lesions of V1. The extent of the scotoma in each case was estimated by mapping the receptive fields of cells located near the lesion border and by histological reconstruction. Two response types were observed among the cells located in the part of MT that corresponds, in visuotopic coordinates, to the lesioned part of V1. Many neurons (62%) had receptive fields that were displaced relative to their expected location, so that they represented the visual field immediately surrounding the scotoma. This may be a consequence of a process analogous to the reorganization of the V1 map after retinal lesions. However, another 20% of the cells had receptive fields centered inside the scotoma. Most of these neurons were strongly direction-selective, similar to normal MT cells. These results show that MT cells differ in their responses to lesioning of V1 and that only a subpopulation of MT neurons can be reasonably linked to residual vision and blindsight.
Subject(s)
Neurons/physiology , Temporal Lobe/physiology , Visual Cortex/physiology , Visual Fields/physiology , Animals , Blindness, Cortical , Brain Mapping , Callithrix , Cerebral Decortication , Photic Stimulation/methods , Scotoma , Visual Cortex/surgery , Visual Pathways/physiologyABSTRACT
The representation of the visual field in visual areas of the dorsolateral, lateral, and ventral cortices was studied by means of extracellular recordings and fluorescent tracer injections in anaesthetised marmoset monkeys. Two areas, forming mirror-symmetrical representations of the contralateral visual field, were found rostral to the second visual area (V2). These were termed the ventrolateral posterior (VLP) and the ventrolateral anterior (VLA) areas. In both areas, the representation of the lower quadrant is located dorsally, between the foveal representation of V2 and the middle temporal crescent (MTc), whereas the representation of the upper quadrant is located ventrally, in the supratentorial cortex. A representation of the vertical meridian forms the common border of areas VLP and VLA, whereas the horizontal meridian is represented both at the caudal border of area VLP (with V2) and at the rostral border of area VLA (with multiple extrastriate areas). The foveal representations of areas VLP and VLA are continuous with that of V2, being located at the lateral edge of the hemisphere. The topographic and laminar patterns of projections from dorsolateral and ventral cortices to the primary (V1) and dorsomedial (DM) visual areas both support the present definition of the borders of areas VLP and VLA. These results argue against a separation between dorsolateral and ventral extrastriate areas and provide clues for the likely homologies between extrastriate areas of different species.
Subject(s)
Brain Mapping/methods , Callithrix/physiology , Visual Cortex/physiology , Visual Fields/physiology , Animals , Callithrix/anatomy & histology , Male , Neural Pathways/physiology , Visual Cortex/anatomy & histologyABSTRACT
The morphological characteristics of the basal dendritic fields of layer III pyramidal neurones were determined in visual areas in the occipital, parietal, and temporal lobes of adult marmoset monkeys by means of intracellular iontophoretic injection of Lucifer yellow. Neurones in the primary visual area (V1) had the least extensive and least complex (as determined by Sholl analysis) dendritic trees, followed by those in the second visual area (V2). There was a progressive increase in size and complexity of dendritic trees with rostral progression from V1 and V2, through the "ventral stream," including the dorsolateral area (DL) and the caudal and rostral subdivisions of inferotemporal cortex (ITc and ITr, respectively). Neurones in areas of the dorsal stream, including the dorsomedial (DM), dorsoanterior (DA), middle temporal (MT), and posterior parietal (PP) areas, were similar in size and complexity but were larger and more complex than those in V1 and V2. Neurones in V1 had the lowest spine density, whereas neurones in V2, DM, DA, and PP had similar spine densities. Neurones in MT and inferotemporal cortex had relatively high spine densities, with those in ITr having the highest spine density of all neurones studied. Calculations based on the size, number of branches, and spine densities revealed that layer III pyramidal neurones in ITr have 7.4 times more spines on their basal dendritic fields than those in V1. The differences in the extent of, and the number of spines in, the basal dendritic fields of layer III pyramidal neurones in the different visual areas suggest differences in the ability of neurones to integrate excitatory and inhibitory inputs. The differences in neuronal morphology between visual areas, and the consistency in these differences across New World and Old World monkey species, suggest that they reflect fundamental organisational principles in primate visual cortical structure.
Subject(s)
Callithrix/anatomy & histology , Cerebral Cortex/cytology , Neurons/cytology , Pyramidal Cells/cytology , Visual Cortex/cytology , Animals , Cerebral Cortex/anatomy & histology , Dendrites/ultrastructure , Fluorescent Dyes , Image Processing, Computer-Assisted , Isoquinolines , Macaca/anatomy & histology , Male , Temporal Lobe/cytology , Visual Cortex/anatomy & histologyABSTRACT
Pyramidal neurones were injected with Lucifer Yellow in cortical slices taken from layer III of the medial subdivision of cytoarchitectonic area 7 (7m) of the macaque monkey. Cross-sectional area, branching complexity and spine density of the basal dendritic fields were determined and compared with those of neurones in other areas of the dorsal processing stream. Layer III pyramidal neurones in area 7m have an average basal dendritic field area of 109.57 +/- 13.03 x 10(3) microm2, which is significantly greater than that obtained for neurones in the lateral intraparietal area (LIP) and area 7a. Moreover, Sholl analyses revealed that neurones in area 7m are significantly more complex in their branching patterns than those in LIP and area 7a. These results reinforce the view that, behind the apparent architectural uniformity of Brodmann's area 7, there is a significant diversity of neuronal structure and function.
Subject(s)
Parietal Lobe/cytology , Pyramidal Cells/cytology , Visual Cortex/cytology , Animals , Cell Size , Dendrites , Fluorescent Dyes , Isoquinolines , Macaca fascicularis , Male , Microinjections , Pyramidal Cells/ultrastructure , Somatosensory Cortex/cytologyABSTRACT
Layer III pyramidal neurons were injected with Lucifer yellow in tangential cortical slices taken from the inferior temporal cortex (area TE) and the superior temporal polysensory (STP) area of the macaque monkey. Basal dendritic field areas of layer III pyramidal neurons in area STP are significantly larger, and their dendritic arborizations more complex, than those of cells in area TE. Moreover, the dendritic fields of layer III pyramidal neurons in both STP and TE are many times larger and more complex than those in areas forming 'lower' stages in cortical visual processing, such as the first (V1), second (V2), fourth (V4) and middle temporal (MT) visual areas. By combining data on spine density with those of Sholl analyses, we were able to estimate the average number of spines in the basal dendritic field of layer III pyramidal neurons in each area. These calculations revealed a 13-fold difference in the number of spines in the basal dendritic field between areas STP and V1 in animals of similar age. The large differences in complexity of the same kind of neuron in different visual areas go against arguments for isopotentiality of different cortical regions and provide a basis that allows pyramidal neurons in temporal areas TE and STP to integrate more inputs than neurons in more caudal visual areas.
Subject(s)
Occipital Lobe/cytology , Parietal Lobe/cytology , Pyramidal Cells/ultrastructure , Temporal Lobe/cytology , Animals , Dendrites/ultrastructure , Macaca fascicularis , Male , Visual Cortex/cytologyABSTRACT
The interhemispheric connections of somatosensory cortex in the gray-headed flying fox (Pteropus poliocephalus) were examined. Injections of anatomical tracers were placed into five electrophysiologically identified somatosensory areas: the primary somatosensory area (SI or area 3b), the anterior parietal areas 3a and 1/2, and the lateral somatosensory areas SII (the secondary somatosensory area) and PV (pairetal ventral area). In two animals, the hemisphere opposite to that containing the injection sites was explored electrophysiologically to allow the details of the topography of interconnections to be assessed. Examination of the areal distribution of labeled cell bodies and/or axon terminals in cortex sectioned tangential to the pial surface revealed several consistent findings. First, the density of connections varied as a function of the body part representation injected. For example, the area 3b representation of the trunk and structures of the face are more densely interconnected than the representation of distal body parts (e.g., digit 1, D1). Second, callosal connections appear to be both matched and mismatched to the body part representations injected in the opposite hemisphere. For example, an injection of retrograde tracer into the trunk representation of area 3b revealed connections from the trunk representation in the opposite hemisphere, as well as from shoulder and forelimb/wing representations. Third, the same body part is differentially connected in different fields via the corpus callosum. For example, the D1 representation in area 3b in one hemisphere had no connections with the area 3b D1 representation in the opposite hemisphere, whereas the D1 representation in area 1/2 had relatively dense reciprocal connections with area 1/2 in the opposite hemisphere. Finally, there are callosal projections to fields other than the homotopic, contralateral field. For example, the D1 representation in area 1/2 projects to contralateral area 1/2, and also to area 3b and SII.
Subject(s)
Chiroptera/anatomy & histology , Corpus Callosum/anatomy & histology , Somatosensory Cortex/anatomy & histology , Animals , Brain Mapping , Chiroptera/physiology , Corpus Callosum/physiology , Somatosensory Cortex/physiologyABSTRACT
Extracellular recordings were made from single and multiple neurons in primary somatosensory cortex (area 3b) of macaque monkeys and flying foxes. When a small region of area 3b (or adjacent area 1) in the opposite hemisphere was cooled, thereby blocking activity that is normally transferred via the corpus callosum, larger receptive fields (RFs) were immediately unmasked for most neurons. RF expansion presumably reflects the expression of afferent inputs that are normally inhibited, suggesting that callosal inputs provide a source of tonic inhibition that contributes to the shaping of neuronal RFs. Quantitative analyses of single neuron responses revealed other effects that were consistent with a release from inhibition, such as increases in response magnitude to stimulation of points within the original RF and decreases in response latency. An unexpected finding was the reversal of these unmasking effects with extended periods of cooling: RFs returned to their original dimensions and within-field response magnitude decreased. In contrast to the initial effects, this reversal of disinhibition cannot be readily explained by an unmasking of previously unexpressed inputs. Any explanation for the reversal requires an increase in the efficacy of interneuron-mediated inhibition, and presumably occurs in response to ongoing, altered patterns of activity.
Subject(s)
Neuronal Plasticity/physiology , Somatosensory Cortex/physiology , Animals , Interneurons/physiology , Macaca , Reaction Time/physiology , Temperature , Time FactorsABSTRACT
The present investigation was designed to determine the organization of somatosensory fields in the lateral sulcus of macaque monkeys using standard microelectrode recording techniques. Our results provide evidence for two complete representations of the body surface. We term these fields the second somatosensory area (SII) and the parietal ventral area (PV) because of their similarities in position, internal organization, and relationship to anterior parietal fields, as described for SII and PV in other mammals. Areas SII and PV are mirror-symmetrical representations of the body surface, sharing a common boundary at the representations of the digits of the hand and foot, lips, and mouth. These fields are located adjacent to the face representations of anterior parietal fields (areas 3b, 1, and 2), and are bounded ventrally and caudally by other regions of cortex in which neurons are responsive to somatic or multimodal stimulation. The finding of a double representation of the body surface in the region of cortex traditionally designated as SII may explain conflicting descriptions of SII organization in macaque monkeys. In addition, the present study raises some questions regarding the designation of serial processing pathways in Old World monkeys, by suggesting that fields may have been confused in studies demonstrating such pathways. We propose that SII and PV are components of a common plan of organization, and are present in many eutherian mammals.
Subject(s)
Brain Mapping , Cerebral Cortex/anatomy & histology , Cerebral Cortex/physiology , Macaca fascicularis/anatomy & histology , Macaca fascicularis/physiology , Somatosensory Cortex/anatomy & histology , Somatosensory Cortex/physiology , Animals , Callithrix/anatomy & histology , Callithrix/physiology , Foxes/anatomy & histology , Foxes/physiology , Macaca/anatomy & histology , Macaca/physiology , Neurons/cytology , Neurons/physiology , Sciuridae/anatomy & histology , Sciuridae/physiology , Species SpecificityABSTRACT
Capsaicin was applied to the exposed radial nerve of adult flying foxes (n = 5) and cats (n = 2) while recording in primary somatosensory cortex from a single neuron with a receptive field on digits 1 or 2. Within four minutes of application of capsaicin the borders of these receptive fields dramatically expanded. In a further four flying foxes it was shown, with subcutaneous delivery just proximal to the receptive fields, that capsaicin need affect only afferents from the region of a neuron's receptive field to induce expansion. Capsaicin applied directly to a nerve, or subcutaneously in high concentrations, is a selective neurotoxin that rapidly prevents the propagation of action potentials in most C-fibres. The result provides a partial explanation for experiments involving the specific and complete denervation of receptive fields of neurons in primary somatosensory cortex. Such denervation does not lead to unresponsiveness but to immediate sensitivity to stimulation of areas surrounding the original fields. Thus it appears that some subclass of capsaicin-sensitive C-fibres provides a primary source for the masking inhibition that normally limits the extent of the receptive fields of cortical neurons.
Subject(s)
Nerve Fibers/physiology , Somatosensory Cortex/physiology , Afferent Pathways/drug effects , Afferent Pathways/physiology , Animals , Capsaicin/administration & dosage , Cats , Denervation , Foxes , Nerve Fibers/drug effects , Neuronal Plasticity/drug effects , Neuronal Plasticity/physiology , Neurons/drug effects , Neurons/physiologyABSTRACT
1. Acute effects of permanent and temporary denervation of the flying fox thumb were examined to test the hypothesis that a large area of skin around the cutaneous receptive field of multiunits (MRF) at a locus in primary somatosensory cortex (SI) supplies viable inputs which can be rapidly unmasked by interruption of the dominant input from the area of the MRF. 2. The immediate effect of amputation of the thumb at loci where the original receptive field was entirely removed was to produce large MRFs on adjacent body areas (wrist, forearm, prowing, and finger membranes). Greatly expanded MRFs were also produced when amputation removed only part of the original MRF at a cortical locus. 3. The probable source of input to account for the new receptive fields is the extensive arborization of ascending projections within the somatosensory pathway, which supply a cortical locus with a potential input from a far larger area than is represented in its normal receptive field. The rapidity with which new or expanded fields are seen following denervation indicates that the normally unexpressed inputs around a receptive field are not only potential inputs but are inherently viable. Hence the most likely explanation for the results of this study is that the effect of the denervation is to disrupt an inhibitory influence that normally has the role of shaping the receptive field. 4. Temporary anesthesia of all or part of a MRF produced similar initial effects to amputation. When responsiveness returned to the locally anesthetized area (after 10-30 min), an expanded MRF persisted for a short time after which the boundaries of the MRF shrank. This rapid reversal suggests that a mechanistic rather than a plastic change is the basis for the acute effect of a small denervation on SI.
Subject(s)
Chiroptera/physiology , Skin Physiological Phenomena , Somatosensory Cortex/physiology , Animals , Denervation , Neural Pathways/physiologyABSTRACT
The short-term effect of total or partial single-digit denervation on receptive fields (RFs) of neurons in somatosensory cortex (area 3b) was examined in five macaque monkeys. In two animals, after denervation by amputation, it was found that electrode positions that initially recorded neurons with RFs on the amputated digit had new RFs extending from the wound. Often the new fields were on adjacent digits. Neurons with initial RFs that were partially amputated, or in some cases close to but not on the amputated digit, showed considerable expansion of the remaining RF. In three monkeys local anesthesia was used to provide a temporary denervation. In these experiments electrodes were placed in equivalent positions in both cortices. The effect on cortex contralateral to the denervation was similar to that seen with amputation. However, after anesthesia returned to the digit, the expanded RFs contracted. In cortex ipsilateral to the denervation, RFs were on the opposite unaffected hand. These also rapidly expanded and then contracted, with the same time course as their counterparts in cortex contralateral to the denervation. Because of the rapidity of the expansion and its temporary nature with short-term denervation, the basis of the effect is probably an unmasking of existing but normally unexpressed connections, which are normally inhibited by the intact output from the denervated area. The wide arborization fields of thalamocortical afferents provide a potential source for the unmasked sensitivity. A mechanism for the inhibition that normally suppresses the expression of large RFs is not readily apparent. However, work in other species suggests that peripheral C fibers provide the primary source of input to central inhibitory circuits.
Subject(s)
Fingers/innervation , Nerve Regeneration/physiology , Neuronal Plasticity/physiology , Peripheral Nerves/physiology , Somatosensory Cortex/physiology , Afferent Pathways/physiology , Animals , Brain Mapping , Dominance, Cerebral/physiology , Macaca fascicularis , Macaca mulatta , Mechanoreceptors/physiology , Skin/innervationABSTRACT
Each half of the body surface is represented topographically in the contralateral cerebral hemisphere. Physiological data are presented showing that homotopic regions of primary somatosensory cortex are linked such that plasticity induced in one hemisphere, in the form of receptive field expansion brought about by a small peripheral denervation, is immediately mirrored in the other hemisphere. Neurons which display the plasticity show no responsiveness to stimulation of the ipsilateral body surface. This suggests that the pathways and mechanisms mediating this transfer are specific to the role of maintaining balance, or integration, between corresponding cortical fields.
Subject(s)
Cerebral Cortex/physiology , Functional Laterality/physiology , Neuronal Plasticity/physiology , Amputation, Surgical , Anesthesia , Animals , Chiroptera , Denervation , Fingers/innervation , Forelimb , Humans , Macaca fascicularis , Somatosensory Cortex/physiology , Toes/innervationABSTRACT
The somatosensory cortex of adult mammals has been shown to have a capacity to reorganize when inputs are removed by cutting afferent nerves or amputating a part of the body. The area of cortex that would normally respond to stimulation of the missing input can become responsive to inputs from other parts of the body surface. Although a few animals have been studied with repeat recording, no attempt has been made to follow the time-course of changes at cortical loci and the immediate effects of a small amputation have not been reported. We have followed the changes in response in the primary somatosensory cortex in the flying-fox following amputation of the single exposed digit on the forelimb. Immediately after amputation, neurons in the area of cortex receiving inputs from the missing digit were not silent but responded to stimulation of adjoining regions of the digit, hand, arm and wing. In the week following amputation, the enlarged receptive fields shrank until they covered only the skin around the amputation wound. The immediate response is interpreted as a removal of inhibition and the subsequent shrinking of the field may be due to re-establishment of the inhibitory balance in the affected cortex and its inputs.
Subject(s)
Chiroptera/physiology , Somatosensory Cortex/physiology , Wings, Animal/physiology , Amputation, Surgical , Animals , Chiroptera/anatomy & histology , Evoked Potentials, Somatosensory , Somatosensory Cortex/pathologyABSTRACT
Epidermal growth factor (EGF) has been shown to enhance both the proliferation and dedifferentiation of thyroid cells in culture, leading to a maintained dedifferentiated state, even in the presence of thyrotropin (TSH). Since this maintained loss of differentiated function is not seen with other mitogens, it may relate to a regulatory role for EGF in thyroid function. Therefore, we have examined the loci affected by the dedifferentiative actions of EGF using porcine thyroid cells in culture. EGF (10 ng/ml) induces a loss of thyrotropin (TSH) receptors with a time course identical to the loss in ability to transport iodide. This could account for the difference in extent of iodide uptake and morphological dedifferentiation seen between TSH- and cAMP-supported cells, although the fact that cAMP-supported cells also dedifferentiate implies a lesion distal to the cyclase. Reciprocal plot analysis of iodide uptake in control and EGF-treated cells shows that EGF increases the Km for iodide transport, corresponding to a decreased affinity of iodide pump sites for iodide. These effects on iodide pump affinity and TSH receptor number may result from reversal of thyroid cell polarity in monolayer culture, or they may be the result of more specific actions of EGF at these loci. It has been possible to discriminate between the proliferative and dedifferentiating actions of EGF using amiloride, a non-specific inhibitor of the Na+/H+ antiporter. An optimum concentration of amiloride (0.1 mM) was able to block EGF-stimulated incorporation of [3H]thymidine into DNA without preventing the blockade of iodide uptake, which implies that dedifferentiation is not a consequence of proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Epidermal Growth Factor/pharmacology , Thyroid Gland/cytology , Amiloride/pharmacology , Animals , Biological Transport, Active/drug effects , Cell Differentiation/drug effects , Cell Division/drug effects , Cyclic AMP/pharmacology , Iodides/metabolism , Kinetics , Receptors, Thyrotropin/metabolism , Swine , Thyroid Gland/metabolism , Thyrotropin/metabolism , Thyrotropin/pharmacologyABSTRACT
Adult Merino ewes were infused via the jugular vein with either saline (n = 5) or epidermal growth factor (EGF) (4.2 micrograms/kg per h, n = 6) for 24 h in either the luteal phase or the follicular phase of the oestrous cycle and reproductive function was examined. Infusion of EGF during the luteal phase caused no detectable change in plasma progesterone or prolactin concentrations over a 7-day period compared with the controls. Infusion of EGF during the follicular phase suppressed the oestrous rise in plasma oestradiol. Luteinizing hormone pulse amplitude was increased and pulse frequency was decreased by the end of the infusion. All control ewes had a pro-oestrous LH surge and mated, but the LH surge and oestrus were prevented by EGF infusion. Nevertheless, plasma progesterone levels rose subsequently in the EGF-infused ewes in parallel with the control ewes, suggesting that the preovulatory follicle had luteinized. Both LH and FSH rose over the 7 days after EGF infusion to levels similar to those in ovariectomized ewes. Thus EGF appears to inhibit follicular oestradiol production, although it does not affect luteal progesterone production or follicular luteinization. We suggest that the alteration in gonadotrophin secretion patterns results from a disturbance of feedback mechanisms between the ovary and the hypothalamopituitary axis, although a direct effect in the brain or the pituitary gland cannot yet be excluded.
Subject(s)
Epidermal Growth Factor/pharmacology , Reproduction/drug effects , Animals , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Follicular Phase , Luteal Phase , Luteinizing Hormone/blood , Progesterone/blood , Prolactin/blood , SheepABSTRACT
Sodium valproate is hepatotoxic in both humans and rat hepatocytes. The toxicity is dose related and frequently associated with simultaneous ingestion of drugs which induce the drug metabolizing system. For these reasons, metabolites of sodium valproate were tested for toxicity using rat hepatocyte cultures. The sodium salts of three metabolites, 2-propylpent-4-enoate, 4-hydroxyvalproate, and perhaps 5-hydroxyvalproate, were toxic in this system. In addition, 2-propylpent-4-enoate was toxic in a dose-related fashion. All are omega and omega-1 oxidation products in the microsome-mediated pathway of valproate metabolism.
Subject(s)
Liver/drug effects , Valproic Acid/toxicity , Animals , Biotransformation , Cells, Cultured , L-Lactate Dehydrogenase/analysis , Male , Rats , Rats, Inbred Strains , Valproic Acid/metabolismABSTRACT
The effects of oxytocin on dispersed luteal cells from human corpora lutea of the menstrual cycle were studied. Oxytocin at a concentration of 4 mi.u./ml produced a slight increase in basal progesterone production. However, higher oxytocin concentrations (400 and 800 mi.u./ml) markedly inhibited both basal and human chorionic gonadotrophin-induced progesterone production. These data provide evidence for an effect of oxytocin on the human corpus luteum. In view of the inhibitory action of oxytocin, increased secretion of this hormone may be important in the demise of the corpus luteum at the end of the menstrual cycle.