Feeding-related dopamine in the amygdala of freely moving rats

Extracellular levels of dopamine (DA) were measured in the central part (the central and intercalated nuclei) of the amygdala (AMY) using microdialysis at 20 min intervals before, during and after 1 h of feeding in 12 h food-deprived rats. The results were compared with the effects of peripheral injections of glucose or a low dose (200 mU) of insulin in non-deprived animals. Feeding caused a 130% increase in extracellular DA. Glucose resulted in an increase in DA levels (+86%). In contrast, insulin caused a decrease of DA (-50%) and metabolites. The results show that natural feeding is associated with an increase in DA turnover in the amygdala, and that peripheral glucose and insulin can affect DA metabolism in the amygdala presumably in response to changes in glucose utilization.     

Post-activation potentiation in the neocortex of awake freely moving rats

Healthy hair samples from golden hamsters were examined for the presence of dermatophytes and non-dermatophytes using baiting technique and direct inoculation. Thirty-four species and 2 varieties attributed to 17 genera were recovered. Paecilomyces variotii (isolated from 84.4% of the examined hair) and Aspergillus niger (81.3%) were the more frequent isolates on Sabouraud's dextrose agar (SDA) without cycloheximide. Our results have clearly demonstrated that the hair of hamster was free from true dermatophytes. Using the dilution plate method many fungal species were isolated from cage material (7 genera and 10 species + 1 variety); from faeces (10 genera and 17 species); from standard chow (3 genera and 6 species) of hamster. P. variotii which was the most frequent fungus in the preceding 3 substrates was completely absent in the presence of cycloheximide in SDA. The present study has demonstrated for the first time the isolation of Trichophyton rubrum from hamster faeces. Also, several saprophytic and cycloheximide resistant fungi were isolated. In the air of hamster cage Cladosporium cladosporioides, Penicillium chrysogenum, Alternaria alternata and Scopulariopsis brevicaulis were the most dominant species on SDA with or without cycloheximide. Using the agar diffusion method, Aloe sap, onion oil, garlic bulb extract and aqueous leaf extracts of Andropogon citratus, Euphorbia sp. and Ruta graveolens were tested for their antifungal activity on 10 fungal species. It was observed that onion oil exhibited a high inhibitory effect against most of the tested fungi.     

Place cells recorded in the parasubiculum of freely moving rats

Previous studies have identified neurons in the hippocampus, subiculum, and entorhinal cortex which discharge as a function of the animal's location in the environment. In contrast, neurons in the postsubiculum and anterior thalamic nucleus discharge as a function of the animal's head direction in the horizontal plane, independent of its behavior and location in the environment. Because the parasubiculum (PaS) has extensive connections, either directly or indirectly, with these structures, it is centrally located to influence the neuronal activity in these areas. This study was therefore designed to determine the types of behavioral and spatial correlates in neurons from the PaS. Single unit recordings were conducted in the PaS of freely moving rats trained to retrieve food pellets thrown randomly into a cylindrical apparatus. A total of 10.3% of the cells were classified as place cells because they discharged in relation to the animal's location in the cylinder. A large percentage of cells (41.4%) were classified as theta cells. The remaining cells had nondiscernable behavioral correlates. Quantitative analysis of the firing rate maps for the place cells showed they had higher levels of background activity and contained larger firing fields than values reported previously for hippocampal place cells. Directional analysis showed that only three out of 16 cells contained a secondary directional correlate; the firing rate for the remaining cells was not affected by the animal's directional heading within the firing field. A time shift analysis, which shifted the spike time series relative to the animal location series, was conducted to determine whether the quality of the location-specific firing could be improved. The time shifts for three different spatial parameters were optimal when cell discharge led the animal's position. Furthermore, the optimal time shifts for two of these parameters (firing area and information content) were less than the optimal shift reported for hippocampal place cells and suggested that PaS cell discharge lagged behind hippocampal place cell activity. Rotation of the cue card with the animal out of view led to near equal rotation of the firing field when the animal was returned to the apparatus. These results indicate that a small population of cells in the PaS encode the animal's location in its environment, although the representation of space encoded by these cells is different from the type of representation encoded by hippocampal place cells.     

Muscarinic elicitation of EEG asymmetry in freely moving rats

A method for determining whether structures distributed along a cell's membrane represent a random spatial distribution is presented in this paper. Two three-dimensional (3-D) images are acquired from one cell by wide-field digital imaging of cells which have been labeled with two different fluorescent antibodies. Prior to spatial analysis, a constrained regularized least squares restoration of the images is performed. This is followed by registration via fiducial markers (dual-labeled beads). A deformable model is then used to map data near the surface to the surface. Finally, each resulting data set is analyzed to determine whether it is spatially random. To do this, we generalize the test for complete spatial randomness of points in a plane, to test voxels distributed along a voxelized membrane in three dimensions. We also test whether the distribution of one protein is independent of the distribution of a second protein. The method is applied to compare the distribution of the protein kinase C to that of vinculin. Vinculin is a protein which anchors intracellular filaments to the cell's plasma membrane. It is also used as a (sparse) membrane marker for the deformable model. Protein kinase C facilitates molecular motors inside the cell. These may be associated with actin and myosin filaments.     

Brain sites involved in the antinociceptive effect of bradykinin in rats

The localization of brain sites where bradykinin (BK) induces its antinociceptive effect in rats, was studied using as index the threshold for the jaw-opening reflex elicited by the dental pulp electrical stimulation test (DPEST). The microinjection of BK into the lateral or fourth cerebral ventricles induced an antinociceptive effect, with Index of Antinociception (IA) of 0.51+/-0.03 and 0.68+/-0.05, respectively. However, microinjections of the peptide into the third ventricle induced a less marked antinociception (IA = 0.28+/-0.08). The brain sites where the microinjection of BK caused an antinociceptive effect were: locus coeruleus, principal nucleus, oral part of the spinal sensorial trigeminal nucleus, and the sensory root of the trigeminal nerve. The antinociceptive effect was more intense when BK (4-16 nmol) was injected into the locus coeruleus. Microinjection of BK (4 nmol) into the fourth ventricle, but not into the locus coeruleus, induced an increase in blood pressure. The microinjection of the peptide into the nucleus tractus solitarius, a site that is also involved in the pressor effect of BK, did not induce an antinociceptive effect. These results indicate that the antinociceptive effect of BK is not related to blood pressure changes. The microinjection of BK into some of the sites involved in the mechanisms of analgaesia, including the periaqueductal gray matter (dorsal, lateral and ventrolateral) and the dorsal raphe nucleus did not induce an antinociceptive effect. The results suggest that the most likely brain sites involved in the antinociceptive effect of BK are the locus coeruleus and the principal sensory trigeminal nucleus. The present results did not exclude the involvement of other brain sites surrounding the lateral and the third ventricles.     

Serotonergic modulation of acetylcholine release from cortex of freely moving rats

The modulation of acetylcholine (ACh) release by 5-HT3 receptor activation was studied using in vivo microdialysis. Spontaneous and K+-stimulated ACh release were measured in frontoparietal cortex and hippocampus of freely moving rats. Two consecutive exposures to high K+ produced ACh release of similar magnitude. In the cortex, serotonin (5-HT) failed to alter spontaneous ACh release, but caused a concentration-dependent decrease of K+-evoked ACh release. Phenylbiguanide (PBG) and m-chlorophenylbiguanide, two selective 5-HT3 agonists, mimicked the 5-HT responses, but 8-hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT1A agonist, was without effect. However, PBG failed to modify K+-evoked ACh release from the hippocampus. Systemic and local administration of a highly selective 5-HT3 antagonist, tropisetron ((3-alpha-tropanyl)1H-indole-carboxylic acid ester) blocked the effect of both 5-HT and PBG. The inhibition of ACh release by PBG was sensitive to tetrodotoxin. These observations provide direct evidence that, in rat cortex, 5-HT modulates in-vivo release of ACh through activation of 5-HT3 receptors.     

NMDA receptor-mediated pilocarpine-induced seizures: characterization in freely moving rats by microdialysis

1. Pilocarpine administration has been used as an animal model for temporal lobe epilepsy since it produces several morphological and synaptic features in common with human complex partial seizures. Little is known about changes in extracellular neurotransmitter concentrations during the seizures provoked by pilocarpine, a non-selective muscarinic agonist. 2. Focally evoked pilocarpine-induced seizures in freely moving rats were provoked by intrahippocampal pilocarpine (10 mM for 40 min at a flow rate of 2 microl min(-1)) administration via a microdialysis probe. Concomitant changes in extracellular hippocampal glutamate, gamma-aminobutyric acid (GABA) and dopamine levels were monitored and simultaneous electrocorticography was performed. The animal model was characterized by intrahippocampal perfusion with the muscarinic receptor antagonist atropine (20 mM), the sodium channel blocker tetrodotoxin (1 microM) and the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine maleate, 100 microM). The effectiveness of locally (600 microM) or systemically (10 mg kg(-1) day(-1)) applied lamotrigine against the pilocarpine-induced convulsions was evaluated. 3. Pilocarpine initially decreased extracellular hippocampal glutamate and GABA levels. During the subsequent pilocarpine-induced limbic convulsions extracellular glutamate, GABA and dopamine concentrations in hippocampus were significantly increased. Atropine blocked all changes in extracellular transmitter levels during and after co-administration of pilocarpine. All pilocarpine-induced increases were completely prevented by simultaneous tetrodotoxin perfusion. Intrahippocampal administration of MK-801 and lamotrigine resulted in an elevation of hippocampal dopamine levels and protected the rats from the pilocarpine-induced seizures. Pilocarpine-induced convulsions developed in the rats which received lamotrigine perorally. 4. Pilocarpine-induced seizures are initiated via muscarinic receptors and further mediated via NMDA receptors. Sustained increases in extracellular glutamate levels after pilocarpine perfusion are related to the limbic seizures. These are arguments in favour of earlier described NMDA receptor-mediated excitotoxicity. Hippocampal dopamine release may be functionally important in epileptogenesis and may participate in the anticonvulsant effects of MK-801 and lamotrigine. The pilocarpine-stimulated hippocampal GABA, glutamate and dopamine levels reflect neuronal vesicular release.     

Effects of prenatal protein malnutrition on hippocampal long-term potentiation in freely moving rats

It has been demonstrated that prenatal protein malnutrition significantly affects hippocampal plasticity, as measured by long-term potentiation, throughout development. This paper focuses on the hippocampal dentate granule cell population response to two separate paradigms of tetanization of the medial perforant pathway in prenatally protein-malnourished and normally nourished adult male rats. The 100-pulse paradigm consisted of the application of ten 25-ms-duration bursts of 400 Hz stimulation with an interburst interval of 10 s. The 1000-pulse paradigm consisted of the application of five 500-ms bursts of 400 Hz stimulation with an interburst interval of 5 s. No between-group differences were obtained for input/output response measures prior to tetanization. No between-group, nor between-paradigm, differences were obtained in the degree of population EPSP slope enhancement. However, in response to both paradigms, prenatally malnourished animals showed significantly less enhancement of the population spike amplitude (PSA) measure than normally nourished animals. Normally nourished animals showed a significantly greater level of PSA enhancement in response to the 100-pulse paradigm than the 1000-pulse paradigm. Prenatally malnourished animals showed no significant differences in the degree of PSA enhancement between the two paradigms. Results indicate that short duration bursts (< or = 25 ms) are more effective in inducing maximal PSA enhancement in normally nourished rats than longer duration stimulus bursts. The apparent inability of prenatally malnourished rats to transfer enhanced cellular activation (population EPSP slope enhancement) into enhanced cellular discharge (PSA enhancement) suggests that a preferential enhancement of GABAergic inhibitory modulation of granule cell excitability may result from the prenatal dietary insult. Such potentiation of inhibitory activity would significantly lower the probability of granule cell population discharge, resulting in the significantly lower level of PSA enhancement obtained from these animals.     

Power spectral electroencephalogram analysis of the effects of ritanserin in freely moving rats during quiet waking

Positron emission tomography (PET) is a radionuclide imaging technique that allows quantitative assessment of regional myocardial function. It is mainly used in clinics to assess viability of dissynergic myocardium, by means of combined images of flow (with ammonia) and metabolism (with fluordeoxyglucose). The mismatch pattern, with an increase in fluordeoxyglucose metabolism in hypoperfused regions, is indicative of viability. The match pattern (a decrease in flow and metabolism in the same areas) is indicative of necrosis. Viability can also be assessed with water or fluordeoxyglucose independently quantified. Other promising methods are based in the study of oxygen consumption with 11C acetate and the study of hypoxia with 18F-misonidazole.     

Comparisons of head direction cell activity in the postsubiculum and anterior thalamus of freely moving rats

Single cells in the rat anterior thalamic nucleus (ATN) and postsubiculum (PoS) discharge as a function of the rat's directional heading in the horizontal plane, independent of its location. A previous study that compared cell firing during clockwise and counterclockwise head turns concluded that ATN 'head direction' (HD) cell discharge anticipates the rat's future directional heading, while PoS HD cell discharge is in register with the rat's current directional heading (Blair and Sharp [1995] J Neurosci 15:6260-6270). In the current study we extend these findings by using a different method of analysis. HD cells in the ATN and PoS were first characterized by three different measures: peak firing rate, range width, and information content. We then examined how these measures varied when cell firing was aligned with past (negative time shift) or future (positive time shift) head direction of the rat. We report that all three measures were optimized when ATN cell firing was aligned with the animal's future directional heading by about +23 msec. In contrast, PoS HD cell firing was optimized when cell firing was aligned with the rat's past head direction by about -7 msec. When the optimal value was plotted as a function of the amount of time spikes were shifted relative to head orientation, the mean ATN function was shifted to the right of the PoS function only at negative time shifts; at positive time shifts the two functions overlapped. Analysis of two recording sessions from the same cell indicated that each cell in a particular brain area is 'tuned' to a specific time shift so that all cells within a brain area are not uniformly tuned to the same time shift. Other analyses showed that the clockwise and counterclockwise tuning functions were not skewed in the direction of the head turn as postulated by Redish et al. ([1996] Network: Computation in Neural Systems 7:671-685) and Blair et al. ([1997] J Neurophysiol 17:145-159). Additional analysis on episodes when the rat happened to continually point its head in the preferred direction indicated that HD cell firing undergoes little adaptation. In the Discussion, we argue that these results are best accounted for by a motor efference copy signal operating on both types of HD cells such that the copy associated with the PoS HD cells is delayed in time by about 30 msec relative to the copy associated with ATN HD cells.     

Light responsiveness of the suprachiasmatic nucleus: long-term multiunit and single-unit recordings in freely moving rats

The suprachiasmatic nuclei (SCN) of the hypothalamus contain a pacemaker that generates circadian rhythms in many functions. Light is the most important stimulus that synchronizes the circadian pacemaker to the environmental cycle. In this paper we have characterized the baseline neuronal firing patterns of the SCN as well as their response to light in freely moving rats. Multiunit and single-unit recordings showed that SCN neurons increase discharge during daytime and decrease discharge at night. Discharge levels of individual neurons that were followed throughout the circadian cycle appeared in phase with the population and were characterized by low discharge rates (often below 1 Hz), with a twofold increase during the day. The effect of light on the multiunit response was dependent on the duration of light exposure and on light intensity, with light thresholds of approximately 0.1 lux. The light response level showed a strong dependency on time of day, with large responsiveness at night and low responsiveness during day. At both phases of the circadian cycle, the response level could be raised by an increase in light intensity. Single-unit measurements revealed that the time-dependent light response of SCN neurons was present also at the level of single units. The results show that the basic light response characteristics that were observed at the multiunit level result from an integrated response of similarly behaving single units. Research at the single-unit level is therefore a useful approach for investigating the basic principles of photic entrainment.     

Heterogeneity of prejunctional neuropeptide Y receptors inhibiting noradrenaline overflow in the portal vein of freely moving rats

Patients with familial amyloidotic polyneuropathy (FAP) showed extremely low plasma apolipoprotein AII (apoAII) levels and apolipoprotein AII/AI (apoAII/AI) ratio while plasma levels of AI, B, CII, CIII, and E were all within normal ranges. To elucidate the reason for these phenomena, we investigated the percent of these proteins contained in high density lipoprotein (HDL) extracted from plasma of FAP patients by ultracentrifugation. The apoAII/AI ratio in extracted HDL was much lower in asymptomatic carriers of FAP as well as FAP patients than that in control subjects. Since a significant amount of apoAII as well as apoAI was recognized in the fraction of the density > 1.21 g/ml in the samples from asymptomatic carriers of FAP and FAP patients, decreased apoAII/AI ratio may result from the increased dissociation of apoAII from HDL during the process of the ultracentrifugation. Electrophoresis of HDL extracted by agarose gel revealed that HDL from asymptomatic carriers of FAP as well as FAP patients increased negative charge, suggesting that nature of HDL itself may change in these subjects. Although urinary excretion of apoAII was increased in carriers of FAP and FAP patients, there was no correlation between plasma and urinary apoAII levels and also no relationship between urinary total protein and apoAII levels. These results suggest that changed affinity of apoAII to HDL may cause the increased secretion of apoAII to the urine and the decreased plasma apoAII level in carriers of FAP and FAP patients.     

Tissue and microdialysate changes after repeated and permanent probe implantation in the striatum of freely moving rats

Neurochemical and morphological effects of repeated microdialysis or permanent microdialysis probe implantations in striatum were studied. The extracellular levels of dopamine did not change between a first and a second probe insertion separated by 2 weeks or at a third dialysis session 2 days later. The 3,4-dihydroxyphenylacetic acid and homovanillic acid levels were similar at the first and second microdialysis session, but decreased at the third. Probes implanted permanently for 2 weeks clogged, and the recovery varied markedly after insertion of new probes. Tyrosine hydroxylase-stained dopamine fibers appeared unaffected after all dialysis sessions, although some swollen fibers were observed surrounding the probes. No change in the glial fibrillary acidic protein staining was seen immediately after the first dialysis session, although 2 weeks later gliosis was observed. After the second and third dialysis a diffuse gliosis was observed, while a glial barrier was seen surrounding the permanently implanted probes. Immediately after the first dialysis session enlarged laminin-stained blood vessels were seen, whereas repeated probe implantation also increased the blood vessel density. Thus, chronic in vivo microdialysis with permanently implanted probes is limited by severe technical problems and marked tissue changes. On the other hand, repeated probe insertion in the same brain site appears to be acceptable for performing chronic microdialysis studies in the same subject, provided neurochemical and morphological changes are taken into consideration.     

The glutamate receptor/NO/cyclic GMP pathway in the hippocampus of freely moving rats: modulation by cyclothiazide, interaction with GABA and the behavioural consequences

Monitoring of extracellular cGMP during intracerebral microdialysis in freely moving rats permits the study of the functional changes occurring in the glutamate receptor/nitric oxide (NO) synthase/guanylyl cyclase pathway and the relationship of these changes to animal behaviour. When infused into the rat hippocampus in Mg2+-free medium, cyclothiazide, a blocker of desensitization of the AMPA-preferring receptor, increased cGMP levels. The effect of cyclothiazide (300 microM) was abolished by the NO synthase inhibitor L-NARG (100 microM) or the soluble guanylyl cyclase inhibitor ODQ (100 microM). During cyclothiazide infusion the animals displayed a pre-convulsive behaviour characterized by frequent "wet dog shakes" (WDS). Neither L-NARG nor ODQ decreased the WDS episodes. Both cGMP and WDS responses elicited by cyclothiazide were prevented by blocking NMDA receptor function with the glutamate site antagonist CGS 19755 (100 microM), the channel antagonist MK-801 (30 microM) or Mg2+ ions (1 mM). The AMPA/kainate receptor antagonists DNQX (100 microM) and NBQX (100 microM) abolished the WDS episodes but could not inhibit the cyclothiazide-evoked cGMP response. DNQX or NBQX (but not MK-801) elevated, on their own, extracellular cGMP levels. The cGMP response elicited by the antagonists appears to be due to prevention of a glutamate-dependent inhibitory GABAergic tone, since infusion of bicuculline (50 microM) caused a strong cGMP response. The results suggest that (a) AMPA/kainate receptors linked to the NO/cGMP pathway in the hippocampus (but not NMDA receptors) are tonically activated and kept in a desensitized state by endogenous glutamate; (b) blockade of AMPA/kainate receptor desensitization by cyclothiazide leads to endogenous activation of NMDA receptors; (c) the hippocampal NO/cGMP system is under a GABAergic inhibitory tone driven by non-NMDA ionotropic receptors; (d) the pre-convulsive episodes observed depend on hippocampal NMDA receptor activation but not on NO and cGMP production.     

The effects of phencyclidine and amphetamine on social behavior in tether-restrained and freely moving rats.

Phencyclidine and amphetamine have been shown to decrease social interactions in humans and animals. However, it has not been known whether the drugged animal withdraws from surrounding undrugged conspecifics, the undrugged conspecifics avoid the drugged animal, or a combinalion of these two possibilities. To explore this issue a novel tether paradigm was used that limited the movemenl of one of the rats to one half of the chamber, such thal the freely moving rat had the option of escaping social interactions. Conditions were included in which both undrugged and drugged rats were the tethered animal. Results indicated that the social withdrawal induced by phencyclidine and amphelamine is a funclion of the freely moving drugged anhnals' voluniary avoidance of social interactions. Results indicate that the tether paradigm successfully pinpoints the source of social withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term potentiation in the neocortex of the adult, freely moving rat

Neocortical preparations have proven highly resistant to the induction of long-term potentiation (LTP), and we have only recently determined the conditions sufficient for the induction of neocortical LTP in the adult, freely moving rat. The stimulation trains must be spaced and repeated over a period of days in order to reach asymptotic levels of potentiation. Here we show that, within these constraints, the neocortex is actually highly responsive. LTP could be induced with as few as one brief high frequency train per day or with extremely low-intensity stimulation trains. We also provide evidence for a critical role for N-methyl-D-aspartate (NMDA) receptor activation in LTP induction in this preparation, and demonstrate that this LTP is input-specific. Control pathways showed no potentiation effects. LTP was found in a monosynaptic and two polysynaptic components (average latencies to peak: 8.1, 15.2 and 20.0 ms) and in the superimposed population spikes. Although LTP could be induced with one train per day or with low-intensity trains, larger and longer-lasting potentiation effects could be induced by increasing the number of trains delivered per session, the number of sessions over which trains were delivered, or the pulse intensity of the trains. The LTP decayed slowly and was still evident 5 weeks later. Administration of the competitive NMDA antagonist 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid blocked the induction of LTP in a dose-dependent fashion and appeared to unmask a depression of both the population spikes and a polysynaptic component. These results indicate that the neocortex is highly sensitive to LTP induction procedures, as long as the stimulation trains are spaced and applied over a period of days. They are also consistent with the view that the neocortex must operate with a slow learning rate to reduce interference effects in memory.     

The neurosteroid pregnenolone sulfate increases cortical acetylcholine release: a microdialysis study in freely moving rats

The effects of pregnenolone sulfate (Preg-S) administrations (0, 12, 48, 96, and 192 nmol intracerebroventricularly) on acetylcholine (ACh) release in the frontal cortex and dorsal striatum were investigated by on-line microdialysis in freely moving rats. Following Preg-S administration, extracellular ACh levels in the frontal cortex increased in a dose-dependent manner, whereas no change was observed in the striatum. The highest doses (96 and 192 nmol) induced a threefold increase above control values of ACh release, the intermediate dose of 48 nmol led to a twofold increase, whereas after the dose of 12 nmol, the levels of ACh were not different from those observed after vehicle injection. The increase in cortical ACh reached a maximum 30 min after administration for all the active doses. Taken together, these results suggest that Preg-S interacts with the cortical cholinergic system, which may account, at least in part, for the promnesic and/or antiamnesic properties of this neurosteroid.     

Kinematics of the freely moving head and neck in the alert cat

In this study we examined connections between the moment-generating capacity of the neck muscles and their patterns of activation during voluntary head-tracking movements. Three cats lying prone were trained to produce sinusoidal (0.25 Hz) tracking movements of the head in the sagittal plane, and 22.5 degrees and 45 degrees away from the sagittal plane. Radio-opaque markers were placed in the cervical vertebrae, and intramuscular patch electrodes were implanted in five neck muscles, including biventer cervicis, complexus, splenius capitis, occipitoscapularis, and rectus capitis posterior major. Videofluoroscopic images of cervical vertebral motion and muscle electromyographic responses were simultaneously recorded. A three-dimensional biomechanical model was developed to estimate how muscle moment arms and force-generating capacities change during the head-tracking movement. Experimental results demonstrated that the head and vertebrae moved synchronously, but neither the muscle activation patterns nor vertebral movements were constant across trials. Analysis of the biomechanical model revealed that, in some cases, modification of muscle activation patterns was consistent with changes in muscle moment arms or force-generating potential. In other cases, however, changes in muscle activation patterns were observed without changes in muscle moment arms or force-generating potential. This suggests that the moment-generating potential of muscles is just one of the variables that influences which muscles the central nervous system will select to participate in a movement.     

Subtype-specific involvement of metabotropic glutamate receptors in two forms of long-term potentiation in the dentate gyrus of freely moving rats

In this study, the role of metabotropic glutamate receptors in N-methyl-D-aspartate receptor-dependent and voltage-gated calcium channel-dependent long-term potentiation in the dentate gyrus of freely moving rats was investigated. Antagonists for group 1 metabotropic glutamate receptors ((S)-4-carboxyphenylglycine), group 1/2 metabotropic glutamate receptors ((RS)-alpha-methyl-4-carboxyphenylglycine) and group 2 metabotropic glutamate receptors ((RS)-alpha-methylserine O-phosphate monophenylester) were used. The N-methyl-D-aspartate receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid, and the L-type voltage-gated calcium channel antagonist, methoxyverapamil were used to investigate the N-methyl-D-aspartate receptor and voltage-gated calcium channel contribution to the long-term potentiation recorded. Field excitatory postsynaptic potential slope and population spike amplitude were measured. Drugs were applied, prior to tetanus, via a cannula implanted into the lateral cerebral ventricle. 200 Hz tetanization produces a long-term potentiation which is inhibited by application of D(-)-2-amino-5-phosphonopentanoic acid and (RS)-alpha-methyl-4-carboxyphenylglycine. In this study, a dose-dependent inhibition of 200 Hz long-term potentiation expression was obtained with (S)-4-carboxyphenylglycine. Long-term potentiation induced by 400 Hz tetanization was not inhibited by D(-)-2-amino-5-phosphonopentanoic acid, although the amplitude of short-term potentiation was reduced. (RS)-alpha-methyl-4-carboxyphenylglycine and (S)-4-carboxyphenylglycine, both in the presence and absence of D(-)-2-amino-5-phosphonopentanoic acid, inhibited the development of 400 Hz long-term potentiation. (RS)-alpha-methylserine O-phosphate monophenylester had no significant effect on long-term potentiation induced by either 200 or 400 Hz tetanization. Application of methoxyverapamil significantly inhibited 400 Hz long-term potentiation, but had no effect on 200 Hz long-term potentiation. These data suggest that 400 Hz long-term potentiation, induced in the presence of D(-)-2-amino-5-phosphonopentanoic acid, requires activation of L-type calcium channels. Furthermore, these results strongly support a critical role for group 1 metabotropic glutamate receptors in both N-methyl-D-aspartate receptor- and voltage-gated calcium channel-dependent long-term potentiation.