Neurochemical Signals Research Articles

Glutamate and vasopressin interact to control scent marking in Syrian hamsters (Mesocricetus auratus)

In Syrian hamsters, vasopressin (AVP) in the medial preoptic-anterior hypothalamus (MPOA-AH) controls a form of scent marking called flank marking. Another neurochemical signal that may interact with AVP to control flank marking is glutamate. We tested the hypothesis that glutamate interacts with AVP in the MPOA-AH to regulate flank marking. On day 1, AVP was microinjected into the MPOA-AH. On day 2, AVP was microinjected as a cocktail combining either AP-5, a NMDA antagonist, or GAMS, a non-NMDA antagonist or propranolol, a β norepinephrine antagonist. On day 3, AVP alone was microinjected. Hamsters engaged in high levels of marking in response to AVP alone or to a combination of AVP and propranolol. In contrast, the frequency of marking was significantly reduced in response to a combination of either AVP and AP-5 or AVP and GAMS. These data support the hypothesis that stimulation of flank marking by AVP within the MPOA-AH requires the activity of glutamate.

Glutamate and vasopressin interact to control scent marking in Syrian hamsters ( Mesocricetus auratus)

In Syrian hamsters, vasopressin (AVP) in the medial preoptic-anterior hypothalamus (MPOA-AH) controls a form of scent marking called flank marking. Another neurochemical signal that may interact with AVP to control flank marking is glutamate. We tested the hypothesis that glutamate interacts with AVP in the MPOA-AH to regulate flank marking. On day 1, AVP was microinjected into the MPOA-AH. On day 2, AVP was microinjected as a cocktail combining either AP-5, a NMDA antagonist, or GAMS, a non-NMDA antagonist or propranolol, a β norepinephrine antagonist. On day 3, AVP alone was microinjected. Hamsters engaged in high levels of marking in response to AVP alone or to a combination of AVP and propranolol. In contrast, the frequency of marking was significantly reduced in response to a combination of either AVP and AP-5 or AVP and GAMS. These data support the hypothesis that stimulation of flank marking by AVP within the MPOA-AH requires the activity of glutamate.

Glutamine cycle enzymes in the crayfish giant nerve fiber: Implications for axon‐to‐glia signaling

Two of the key enzymes involved in glutamate metabolism, glutaminase and glutamine synthetase, were quantitatively localized to axons and glia of the crayfish giant nerve fiber by immunocytochemistry and electron microscopy of antibody-linked gold microspheres. In Western blots, rabbit antisera for glutamine synthetase and glutaminase specifically recognized crayfish polypeptides corresponding approximately in size to subunits of purified mammalian brain enzymes. Glutamine synthetase immunoreactivity was found to be 11 times greater in the adaxonal glial cells than in the axon. Glutaminase immunoreactivity was found in somewhat greater concentration (2.5:1) in glia as compared to axoplasm. Glutamate immunoreactivity also was evaluated and found to be present in high concentration in both glia and axons, as might be expected for an important substrate of cellular metabolism. Using radiolabeled substrates it was demonstrated that glutamine and glutamate were interconverted by the native enzymes in the intact crayfish giant nerve fiber and that the formation of glutamine from glutamate occurred in the axoplasm-free nerve fiber, the cellular component of which is primarily periaxonal glia. The results of this investigation provide immunocytochemical and metabolic evidence consistent with an intercellular glutamine cycle that modulates the concentration of periaxonal glutamate and glutamine in a manner similar to that described for perisynaptic regions of the vertebrate central nervous system. These findings further corroborate previous electrophysiological evidence that glutamate serves as the axon-to-glial cell neurochemical signal that activates glial cell mechanisms responsible for periaxonal ion homeostasis.

Glucose-sensitive neurons of the globus pallidus: I. Neurochemical characteristics

The lateral hypothalamic area (LHA) and globes pallidtaz (GP) are basically involved in the regulation of feeding and metabolic processes. In the LHA, glucose-sensitive (GS) neurons were described: their activity was found to be specifically suppressed by electrophoretic application of glucose, and these neurons appeared to be also influenced by various feeding-associated neurochemical signals. The main goal of the present experiments was to examine whether similar GS neurons exist in the GP. In addition, neurochemical attributes of the cells were also tested. In anesthetized rats and anesthetized or awake monkeys, single-neuron activity of the GP was recorded by means of carbon fiber multibarreled microelectrodes and the effects of glucose, glutamate (Gt), GABA, dopamine (DA), noradrenaline (NA) and acetylcholine (Ach) were studied. In both the rat and monkey GP, approximately 12% of the neurons examined responded, with inhibition, to glucose. GP neurons, in a high proportion, were also inhibited by GABA and NA. After application of Gt, DA, or Ach, activity increase or decrease occurred. GS neurons exhibited remarkable sensitivity to these neurochemicals previously identified as neurotransmitters of the complex pallidal, extrapyramidel-limbic neuron loops. The results, along with previous data, indicate that GS cells of the GP, while possessing complex neurochemical characteristics, may belong to a hierarchically organized central glucose-monitoring system essential in the regulation of feeding.

Effect of naloxone and antidepressants on hyperphagia produced by peptide YY

Central injection of peptide YY (PYY) elicits a powerful feeding response with a short latency in satiated rats. Because of this effect, PYY has been implicated as a neurochemical signal in bulimia nervosa. Serotonin agonists and opioid antagonists induce anorectic effects upon feeding behavior in humans and animals. Therefore, to investigate a possible interaction between PYY-induced eating and these anorexigenic agents rats were given injections of either naloxone (100 μg/3 μl, ICV, and 10 mg/kg, SC), fluoxetine (3–30 μg/3 μl and 5–10 mg/kg, IP), or clomipramine (3–30 μg/3 μl and 5–10 mg/kg, IP) prior to fourth ventricular injections of PYY (15 μg/18 μl). Central and peripheral naloxone and IP but not central injections of fluoxetine blocked PYY-induced intake. Clomipramine had no effect. This suggests that PYY-stimulated feeding may require the action of endogenous opioids and may be inhibited by serotonergic function.

A morpho-functional investigation of the interaction of neurochemical signals in neurons of the cerebral cortex of rats.

A morpho-functional investigation of the interaction of neurochemical signals in neurons of the cerebral cortex of rats.

Plasticity and Differentiation of Retinal Precursor Cells

Publisher Summary This chapter describes plasticity and differentiation of retinal precursor cells. Retinal photoreceptors are unique cells, whose high degree of specialization and differentiation can be recognized in their shape and organization, in the presence of many unique proteins, and in their physiological activities. Visual perception is based on the cortical processing of neurochemical signals generated within the retina in response to the light entering the eye from the external world. The photoreceptors are the retinal cells that set this visual process in motion by transducing light into neurochemical signals. Most vertebrate retinas have two major photoreceptor subtypes, the rods and the cones, which share many features but also have distinctive structural, chemical, and functional differences. One of the most remarkable aspects of the differentiation of isolated photoreceptor precursor cells in culture is their capacity to develop and maintain, even when grown in the absence of intercellular contacts, a highly elongated, compartmentalized, and polarized pattern of organization.

Ultrastructural changes in synapses of cortical neurons following combined applications of glutamate and noradrenaline

The dimensions of postsynaptic densities (PSD) of axodendritic synapses in the sensorimotor region of the rat neocortex were determined following multiple paired microiontophoretic applications of L-glutamate (Gl) and noradrenaline (NA) using electron microscopy. It was established that combined applications of Gl and NA induce a statistically significant increase in the thickness of the PSD. In this case, the intensity of the structural changes depends on the delay time (within the range of 0–5 sec) of NA action in relation to Gl. The strongest modification in PSD was observed whenever the second neurochemical signal was received at the amount of cessation of the neuronal response to the action of the first transmitter.

Role of the time interval in the effect of neurochemical signals in the changes in the ultrastructure of cortical synapses.

Role of the time interval in the effect of neurochemical signals in the changes in the ultrastructure of cortical synapses.

Dependence of the ultrastructural changes in cortical synapses on the time interval between associated neurochemical signals.

Dependence of the ultrastructural changes in cortical synapses on the time interval between associated neurochemical signals.

Posterior midbrain-induced locomotion

The purpose of this study was to determine the nature of the neurochemical signals which impinge on the mesencephalic locomotor region (MLR) to produce locomotion in the rat. Injections of GABA antagonists into NADPH diaphorase-positive regions (PPN) were found to induce locomotion for short episodes (5–30 sec) which were repeated for several minutes (1–40 min). Such activity was blocked by injections of GABA and the GABA agonist, muscimol. Locomotion was induced by injection of substance P (SP), which also produced short, repeated episodes of locomotion. The more potent excitatory amino acid agonist, n-methyl-d-aspartic acid (NMDA), however, did produce dose-dependent, long-lasting (20 sec–5 min) locomotor episodes which were repeated over prolonged periods at the higher concentrations used (2–24 min). Additional injections of NMDA could drive stepping from a walk to a trot to a gallop. The effects of NMDA were blocked by injections of the excitatory amino acid antagonist, aminophosphonovalerionic acid (APV) (1–10 mM). Preliminary evidence suggests that carbachol (10–50 mM), a cholinergic agonist, inhibits NMDA-induced increases in muscle tone and episodes of stepping. The effect of carbachol was blocked by the cholinergic antagonist, atropine.

Thermoperiod and photoperiod interact to affect the phase of the plasma melatonin rhythm in the lizard, Tiliqua rugosa

Rhythms of plasma melatonin levels were determined in lizards ( Tiliqua rugosa) subjected to 6 h thermocycles (6 h, 33°C thermophase; 18 h, 15°C cryophase) placed at 4 different phases of a 12 h photocycle (12 h light: 12 h dark). The peak of the melatonin rhythm was either shifted at different rates, or inhibited by the light phase of the photocycle, depending upon the phase relationship between the thermocycle and the photocycle. The results indicate that the pineal organ of ectotherms is part of a circadian pacemaker system, transducing photothermal environmental information into a neurochemical signal.

Evidence that hypothalamic neuropeptide Y secretion decreases in aged male rats: implications for reproductive aging.

The decrease in circulating testosterone and LH titer that occurs in aged male rats may in part be a consequence of decreased excitatory neurochemical signals that promote the episodic discharge of LHRH from the hypothalamus. In view of evidence that neuropeptide Y (NPY) stimulates the release and potentiates the action of LHRH on LH secretion, the present studies investigated age-related changes in the concentrations of NPY in individual hypothalamic nuclei and in the ability of hypothalamic tissues to release NPY in vitro. Compared with tissues of 2.5-month-old male rats, medial basal hypothalamic tissues of 13-month-old rats released significantly less NPY in response to K+ depolarization. In contrast, K+-evoked LHRH release from the same tissues was unimpaired. Aged male rats also exhibited markedly reduced concentrations of NPY in the median eminence and in the arcuate, medial preoptic, suprachiasmatic, paraventricular, dorsomedial, and ventromedial hypothalamic nuclei, which are sites of NPY perikarya and nerve terminal networks. These neurochemical changes occurred in association with decreased serum testosterone and LH levels. These findings demonstrate a widespread age-related decline in NPY levels and release in the hypothalamus, which may be responsible for the reduction in testosterone secretion and may contribute to the decline in reproductive function in aged male rats.

Food deprivation and ingestion induce reciprocal changes in neuropeptide Y concentrations in the paraventricular nucleus

We have studied the effects on neuropeptide Y (NPY) concentration in six hypothalamic nuclei, viz. medial preoptic area (MPOA), paraventricular nucleus (PVN), median eminence (ME), arcuate nucleus (ARC), ventromedial nucleus (VMN) and dorsomedial nucleus (DMN) of food deprivation (FD) for 2, 3, or 4 days or FD for 4 days followed by one day ad lib food intake (FI) in male rats. Hypothalamic nuclei were microdissected by the technique of Palkovits and processed for measurement of NPY immunoreactivity by RIA. NPY-like immunoreactivity in the ME, VMN and DMN was unaffected by FD or FI, but the remaining three nuclei—the ARC, MPOA and PVN—displayed a different pattern of changes in NPY levels in response to either FD or FD followed by FI. In the ARC, NPY levels rose significantly at day 3 and 4 after FD and remained elevated even after one day of FI. In the MPOA, while FD for 4 days had no effect, NPY concentration increased significantly in response to FI. In contrast, in the PVN, a site implicated in the control of feeding behavior, the NPY response to FD and FI was markedly different. FD elicited a gradual, time-related increase in NPY levels to reach highest concentration on day 4 and thereafter, following one day of FI, NPY levels fell dramatically to the range found in control satiated rats. These results show that (1) NPY levels display site-specific changes in response to FD and FI; (2) a dramatic reciprocal change in the PVN NPY levels occurred in response to disturbances in the daily food intake as produced by sequential FD and FI; (3) other hypothalamic sites, such as the ARC and MPOA, displayed only unidirectional increments in response to FD and FI. The observation of site-specific changes in the PVN NPY levels further support the hypothesis that NPY may be a physiological neurochemical signal in the PVN that normally evokes feeding in the rat.

Inhibitory influence of corticotropin releasing factor on components of sexual behaviour in the male rat

Acute microinfusions of ovine corticotropine releasing factor (CRF) into the third cerebral ventricle (III vent.) of sexually experienced male rats produced a dose-dependent suppression of masculine sexual behaviour. This inhibition of male sexual performance induced by CRF could be reversed by simultaneous infusions of naloxone, the opiate receptor antagonist, which when infused without CRF facilitated copulatory performance. These findings suggest that CRF can exert drastic effects on male reproductive behaviour through mechanisms which involve the activation of opioid pathways within the central nervous system. This CRF-linked neurochemical signal may mediate some of the well-known deleterious effects of stressful and noxious stimuli on reproductive function.

FMRF-amide-like substances in the leech. I. Immunocytochemical localization

FMRF-amide-like immunoreactivity (FLI) was localized to approximately 50 neurons in each segmental ganglion of the medicinal leech using immunocytochemical techniques. Although most of these neurons were iterated in each segmental ganglion, some were more restricted in their segmental distribution. The head and tail ganglia likewise contained numerous FMRF-amide-like immunoreactive cells. In addition to cell bodies, many nerve processes and varicosities were also immunoreactive throughout the ganglion. All labeling of FLI was blocked by preabsorption of the anti-FMRF-amide antiserum with synthetic FMRF-amide. Using a combination of Lucifer Yellow cellular injection and indirect immunofluorescence techniques, we identified several of the neurons possessing FLI. Identified neurons included excitatory motor neurons (HE, RPE, LPE, AE, and L), the HA modulatory neuron, interneuron cell 204, and cells of unknown function (AP). The processes of HE motor neurons and HA modulatory neurons which innervate the heart tubes were also immunoreactive. These results indicate a role for FMRF-amide-like substances as neurochemical signals in the leech.

Acute changes in brain tryptophan and serotonin after carbohydrate or protein ingestion by diabetic rats.

In normal, fasting rats, intubation with glucose did not alter serum tryptophan, but it did reduce serum concentrations of the large neutral amino acids, tryptophan's competitors for brain uptake. The serum ratio of tryptophan to the sum of these competitors, which predicts brain tryptophan uptake, was thus increased. Brain tryptophan, serotonin (which is synthesized from tryptophan), and 5-hydroxyindoleacetic acid levels also increased. Such increases in brain serotonin are potentially important, since serotonin is a neurotransmitter. Changes in its level may indicate altered release by neurons and, thus, modified brain function. In contrast, glucose intubation of fasting streptozotocindiabetic rats elicited only a small increase in the serum tryptophan ratio. Brain tryptophan increased slightly; no changes occurred in brain serotonin or in 5-hydroxyindoleacetic acid. Similar effects were noted when fasting diabetic rats consumed a single, carbohydrate meal. However, brain indoles did increase after carbohydrate ingestion in diabetic rats that received an insulin injection at the time food was presented. Effects of ingesting a protein-containing meal were also studied. In normal rats, consumption of this meal increased the serum tryptophan ratio slightly. Brain tryptophan and serotonin levels were unchanged. In diabetic rats, ingestion of the protein-containing meal often lowered the serum tryptophan ratio. Brain tryptophan also fell in diabetic rats when the serum tryptophan ratio was reduced, but brain 5-hydroxyindoles did not fall. The data demonstrate that the absence of a carbohydrate-induced increment in brain indole levels follows indirectly from the absence of the insulin-induced rise in the serum tryptophan ratio. The diabetic rat's inability to experience normal carbohydrate-induced increments in brain serotonin suggests that brain functions, normally dependent on such neurochemical signals, may be abnormal.

Neuroendocrine Communication (Neurohormonal, Neurohumoral, and Intermediate)

The presence of synaptic or synapse-like (synaptoid) configurations in electron micrographs of a variety of endocrine organs leads to the conclusion that at least some of the neurochemical signals in operation are the same as those in regular neuron-to-neuron communication. This kind of morphological information is substantiated by physiological data—for example, in the case of the beta cells of the endocrine pancreas. The adrenergic nature of the transmitter operating at neuron terminals that are in contact with some of these glandular elements is suggested by their ultrastructure. The specific fluorescence for catecholamine displayed at these sites increases after the administration of monoamine oxidase inhibitors, and the measurable rise in catecholamine content is accompanied by a stimulation of insulin secretion. Alloxan-treated animals show fine structural alterations in the terminals that are indicative of neuronal hyperactivity in conjunction with stimulation of insulin secretion. In conclusion, multiple avenues have been acquired in the course of specialization that allow for considerable versatility in neuroendocrine mediation. The increasing familiarity with the dynamics of cellular interaction now directs attention to the exploration of biochemical events at the receptor site, the results of which will transcend the scope of neuroendocrinology.