The effect of picrotoxin and the duration of conditioning on the induction of associative long-term potentiation in field CA1 of the mouse hippocampus in vitro

Field potentials were recorded from stratum radiation of CA1 region of mouse hippocampal slices in response to distal Schaffer collateral stimulation (S2). Associative long-term potentiation (ALTP) was induced by simultaneous tetanization of C2 together with proximal Schaffer collateral tetanization (C1). Effects of simultaneous (C1 and C2) and successive (C1 precedes C2 for 200 ms) activation of two inputs were compared. Tetanizations with a foregoing activation of Cl ("conditioning" input) were more effective in experiments with short (30 ms, 100 Hz) trains of pulses. Simultaneous activation of two inputs was more effective when S1 input was tetanized with long (150 ms) trains or synaptic inhibition was blocked by picrotoxin (5.10(-6mM). It is suggested that ALTP induced by short trains of pulses with intervals of 200 ms is a more adequate model of memory than that induced by long-lasting tetanic trains.     

Isometric contraction of the abductor digiti minimi muscle in man

Isometric contraction of the abductor digiti minimi muscle (ADM) has been studied in six normal subjects. Twitch contraction times of ADM ranged from 60 to 68 ms and twitch torque ranged from 2·33 to 6·24 × 10^-3 Nm. In three subjects torque declined by an average of 31% after tetanization at 50 Hz for 30 seconds but there was no similar diminution in the evoked muscle action potential suggesting that the fatigue arose from intrinsic muscular mechanisms. A marked decline in tetanic torque occurred with continued tetanization in two subjects for a total of five minutes, but this change was accompanied by a decrease in the muscle action potential. In six subjects threshold stimulation to the ulnar nerve at the wrist and to various sites over the motor point of ADM allowed 55 threshold twitch contractions to be identified after averaging. A unimodal range of contraction times ranging from 40-100 ms was found and this was confirmed by additional experiments in two subjects in whom 30 threshold twitch contractions were identified using a needle electrode to stimulate various sites in the motor point. Tetanization at 50 Hz was performed using threshold stimulus levels. Nine threshold tetanic contractions were evoked in two subjects. In eight tetanic torque progressively fatigued to between 14 and 20% within 60-90 seconds, but, in one tetanic contraction, torque proved relatively fatigue resistant. These results suggest that there is a homogeneous group of motor units in ADM (with respect to contraction time) and that this group contains what are probable fast twitch fatigue sensitive and fatigue resistant motor units. No evidence of a distinct group of slow twitch units was found.     

Anisomycin blocks the late phase of long-term potentiation in the dentate gyrus of freely moving rats

Freely moving rats, chronically implanted with stimulation electrodes in the medial entorhinal cortex and recording electrodes in the dentate gyrus, received two 400 micrograms intraventricular injections of anisomycin during a tetanization procedure that induced a long-lasting potentiation (72 hours) of the monosynaptic field potential. Inhibition of protein synthesis during the tetanization procedure did not immediately influence the induction of long-term potentiation (LTP). However, 3-4 hours after the beginning of tetanization the potentiation effect decayed progressively and was abolished totally during the remaining 7 day observation period. In control experiments anisomycin did not affect the slope of field EPSP's and produced a reversible depression of the population spike amplitude. These data indicate a relatively specific effect of the protein synthesis inhibitor on mechanisms involved in a late phase of LTP stabilization.     

Functional polymorphisms of the cytochrome P450 1A2 (CYP1A2) gene and prolonged QTc interval in schizophrenia

CYP1A2 is an important inducible enzyme involved in the metabolism of antipsychotics. This study examined two functional polymorphisms in the gene as potential markers in predicting prolongation of QTc interval in patients treated with antipsychotics. QT intervals were measured by 12-lead electrocardiography (ECG) for patients with a DSM-IV diagnosis of schizophrenia. Genomic DNA extracted from venous blood were genotyped for the two polymorphisms by PCR-RFLP. Statistically significant result for CYP1A2(*)1F was noted for all patients receiving chlorpromazine equivalent doses of above 300 mg and also for a further subgroup on antipsychotics known to be CYP1A2 substrates (p=0.007, mean QTc in ms for A/A: 395.5+/-15.1, A/C: 425.7+/-25.1, C/C: 427.3+/-20.7). For CYP1A2(*)1C, there was no statistically significant association between genotypes and mean QTc interval. Overall, there was a trend of those with the C allele of the CYP1A2(*)1F polymorphism having longer QTc intervals. The results of this study suggest that the CYP1A2(*)1F polymorphism may contribute to the risk of developing prolonged QT-interval in patients who are treated with higher doses of antipsychotics.     

Long-lasting potentiations evoked by a brief heterosynaptic tetanus in the guinea pig dentate gyrus in vitro

The heterosynaptic effects induced by a brief afferent tetanization in the molecular layer of the dentate gyrus were investigated in the guinea pig hippocampal slice preparation using extracellular recording technique. At a brief interval (5 ms) between a single stimulation of the test afferents and the tetanus evoked in the conditioning afferents, a long-lasting (greater than 1 h) potentiation of the test field excitatory postsynaptic potential (EPSP) initial slope and amplitude was observed. This potentiation was occluded by prior homosynaptic tetanization of the test afferents, suggesting that it represents long-term potentiation (LTP). Thus, in the dentate gyrus, a single activation of a single test EPSP suffices to induce LTP when coinciding in time with a brief tetanus to other afferents. When not temporally paired with the test stimulation, i.e. at longer test-conditioning intervals (greater than 50 ms), the conditioning tetanus also elicited a long-lasting potentiation of the test field EPSP. This potentiation was, however, seen as a prolongation of the rising phase with no change in the field EPSP initial slope, and may represent a potentiation distinct from LTP.     

Paired-pulse plasticity in the strength and latency of light-evoked lateral inhibition to retinal bipolar cell terminals

Synapses in the inner plexiform layer of the retina undergo short-term plasticity that may mediate different forms of adaptation to regularities in light stimuli. Using patch-clamp recordings from axotomized goldfish Mb bipolar cell (BC) terminals with paired-pulse light stimulation, we isolated and quantified the short-term plasticity of GABAergic lateral IPSCs (L-IPSCs). Bright light stimulation evoked ON and OFF L-IPSCs in axotomized BCs, which had distinct onset latencies (～50-80 and ～70-150 ms, respectively) that depended on background light adaptation. We observed plasticity in both the synaptic strength and latency of the L-IPSCs. With paired light stimulation, latencies of ON L-IPSCs increased at paired-pulse intervals (PPIs) of 50 and 300 ms, whereas OFF L-IPSC latencies decreased at the 300 ms PPI. ON L-IPSCs showed paired-pulse depression at intervals <1 s, whereas OFF L-IPSCs showed depression at intervals ≤1 s and amplitude facilitation at longer intervals (1-2 s). This biphasic form of L-IPSC plasticity may underlie adaptation and sensitization to surround temporal contrast over multiple timescales. Block of retinal signaling at GABA(A)Rs and AMPARs differentially affected ON and OFF L-IPSCs, confirming that these two types of feedback inhibition are mediated by distinct and convergent retinal pathways with different mechanisms of plasticity. We propose that these plastic changes in the strength and timing of L-IPSCs help to dynamically shape the time course of glutamate release from ON-type BC terminals. Short-term plasticity of L-IPSCs may thus influence the strength, timing, and spatial extent of amacrine and ganglion cell inhibitory surrounds.     

Long-term potentiation recruits a trisynaptic excitatory associative network within the mouse dentate gyrus

Granule cells of the hippocampal dentate gyrus receive two powerful excitatory inputs: the perforant path, originating from the entorhinal cortex, and the associational pathway, originating from mossy cells, the principal neurons of the dentate gyrus hilus. We examined the electrophysiological properties of the less well-studied associational pathway and its interaction with the perforant path in the intact mouse hippocampus and then tested homosynaptic, trans-synaptic and associative long-term potentiation of these pathways. The associational pathway was either monosynaptically activated by stimulation within the inner molecular layer or trisynaptically activated after stimulation of the perforant path. Laminar profiles of extracellularly recorded associational pathway field potentials demonstrated a bell-shaped curve with a peak in the inner molecular layer. Tetanization of the perforant path induced not only homosynaptic potentiation of the perforant path (162.4 +/- 6.7% at 0.5-1.5 h after tetanus) but also heterosynaptic potentiation of the associational pathway (115.7 +/- 4.9%). Direct tetanization of the associational pathway within the inner molecular layer was ineffective in either the septo-temporal (97.2 +/- 4.5%) or temporal-septal (104.4 +/- 4.6%) direction. In contrast, conjoint tetanization of the associational pathway with the perforant path potentiated the associational pathway responses in both the septo-temporal (123.4 +/- 5.8%) and the temporal-septal (124.8 +/- 7.3%) directions. Paired-pulse facilitation was attenuated by long-term potentiation in the perforant path and the associational pathway, suggesting pre-synaptic involvement. These results demonstrate that long-term potentiation of the associational pathway and the perforant path is a product of the network properties of the dentate gyrus rather than of each monosynaptic input alone. The architecture of this neural network may be designed for flexible dynamic associations of the afferent perforant path inputs to configure encoded information within hippocampal neuronal ensembles.     

Role of cortical inhibition in heterosensory interaction of neurons of the sensomotor cortex of the cat

Background and evoked neuronal activity of the sensorimotor cortex was studied in cats under chloralose anaesthesia. Click, flashes and shocks applied to the contralateral forepaw were used as stimuli. Paired heteromodal stimuli were presented with interstimulus intervals of 0, 100, 200, 300 and 400 ms. Stimuli of different modality completely or partly blocked the response to the testing stimulus when the interstimulus interval was 100-200 ms. The maximum response to the second stimulus followed 200-300 ms after the first stimulus. To study the intercortical mechanisms of heterosensory interaction picrotoxin (antagonist of inhibitory neurotransmitter) was locally applied to the studied neuron. Picrotoxin application produced reduction of the blocking period after the conditioning stimulus and appearance of a response to the testing stimulus at shorter interstimulus intervals compared with those observed before application. In some cells an increase in the number of spikes in a burst at one interstimulus interval or an even rise in the response at several interstimulus intervals were observed. The question about the role of intracortical inhibitory influences on the mechanisms of heterosensory interaction on neurons of the sensorimotor cortex is discussed on the basis of the obtained data.     

The effect of electrical stimulation of the locus coeruleus on the neuronal activity of the parietal associative cortex

In experiments performed on cats operated under ketamine anaesthesia and subsequently immobilized by myorelaxin it was demonstrated that locus coeruleus (LC) being stimulated by a train of pulses can exert influence on 79% of parietal cortex neurons. Inhibition of the background activity for 300-700 ms or a decrease in its frequency by 16-32% were observed in them after the LC stimulation. During intracellular recording neurons with background activity and "silent" neurons responded to LC stimulation by hyperpolarization (5-7 mV) lasting for 120-500 ms with latency of 30-90 ms. The duration of the inhibitory pause in background activity caused by transcallosal stimulation increased by 50-200 ms due to conditioning stimulation of LC. The duration of IPSPs evoked by transcallosal stimulation also increased by 50-100 ms under the influence of LC stimulation. It is concluded that the influence of LC stimulation on the activity of the parietal cortex neurons can be exerted either directly as inhibition of background activity and hyperpolarization or as modulation of effects of other neurotransmitters.     

Impaired synaptic plasticity in a rat model of tuberous sclerosis

Tuberous sclerosis complex (TSC) is a common hereditary disorder caused by mutations in either the TSC1 or TSC2 genes, and characterized by severe epilepsy, cerebral hamartomas and mental retardation. We have used rats that are heterozygous for an autosomal-dominant germline mutation in the TSC2 gene (TSC2+/- rats) to examine the consequences of TSC2 mutations for hippocampal synaptic plasticity. While basal synaptic transmission in the Schaffer collateral-CA1 synapse was not altered, paired-pulse plasticity was significantly enhanced in TSC2+/- rats (interpulse intervals 20-200 ms). Moreover, TSC2+/- rats exhibited a marked reduction of different forms of synaptic plasticity. Long-term potentiation (LTP) elicited following high-frequency tetanization of Schaffer collaterals was significantly decreased from 1.45 +/- 0.05-fold potentiation to 1.15 +/- 0.04 (measured after 60 min). This difference in LTP levels between TSC2+/- and wild-type rats also persisted in the presence of the gamma-aminobutyric acid (GABA)(A) receptor antagonist bicuculline. In addition to changed LTP, the level of long-term depression (LTD) elicited by different forms of low-frequency stimulation was significantly less in TSC2+/- rats. These results suggest that TSC2 mutations may cause hippocampal synapses to lose much of their potential for activity-dependent synaptic modification. An understanding of the underlying molecular pathways may suggest new therapeutic approaches aimed at inhibiting the development of the profound mental retardation in TSC.     

Suppression of the "fast" IPSP when superimposed on the "slow" IPSP as a possible cause of priming in the mouse hippocampus

Extra- and intracellular responses of the mouse hippocampus were recorded at CA1 region after stimulation of two independent inputs from the Schaffer collateral/commissural fibres: conditioning or priming input (C1) and testing or primed one (C2). Duration and amplitude of primed field potentials (FP) and excitatory postsynaptic potentials (EPSP) as well as amplitudes of early (IPSPa) and late (IPSPb) components of inhibitory postsynaptic potentials (IPSP) were measured with variation of C1-C2 intervals from 0 to 1 s. An increase in the FP duration as well as EPSP duration and amplitude and suppression of the IPSP amplitude occurred after conditioning with intervals of 50-500 ms, maximal effect was at 200 ms ("priming" effect). These changes correlated with the amplitude of priming IPSPb. The most prominent effect was observed in cells with hyperpolarizing IPSPa. It is assumed that primed FP and EPSP increase due to suppression of the primed IPSPa, when it is superimposed on the priming IPSPb.     

Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro

Long-term potentiation (LTP) with its extremely long duration has been frequently regarded as an elementary mechanism of information storage in the nervous system or at least as a suitable model for the study of mechanisms underlying functional plasticity and processes of learning and memory formation. Considering the necessity of an increased protein synthesis for memory consolidation and for the maintenance of LTP in granular synapses in vivo it was of interest to determine whether the LTP of the CA1 region of the hippocampus depends on protein synthesis as well. For the solution of this question anisomycin (ANI), a reversible blocker of protein synthesis, was used at a concentration of 20 microM, which blocked the [3H]leucine incorporation in hippocampal slices by at least 85%. It has been shown that in the CA1 region in vitro the maintenance of LTP (i.e. a late phase greater than 5 h) depends on an ongoing protein synthesis. A 3-h treatment with ANI immediately following multiple tetanization resulted in gradually developing loss of field excitatory postsynaptic potential (EPSP) and population spike (PS) potentiation (15 +/- 19% increase of the PS instead of the 96 +/- 14% increase in non-treated control experiments at the 8th h after tetanization). Furthermore, a late PS potentiation (greater than 6 h) of a second non-tetanized pathway to CA1 pyramidal cells has been observed (increase by 64 +/- 18% at the 8th h) for the first time. This potentiation was ANI-sensitive as well and suggests that the maintenance of LTP is dependent on a postsynaptic mechanism.     

Role of direct and feedback inhibition in the effect of "priming" in hippocampus slices]

Field potentials (FP) were recorded from radial and pyramidal layers of the mice hippocampus after conditioning and testing stimulations of the Schaffer collaterals. The effect of a preliminary conditioning stimulus on the tested responses (the "priming" effect) was studied for different testing intensities and interstimulus intervals of 50 to 5000 ms. Two series of experiments were conducted. In the first series the influence of the conditioning stimulus delivered with the interval of 200 ms on the testing stimuli of various intensities was studied. The duration of the testing FP in the radial layer was measured. The plot of the FP duration against the stimulus strength revealed three regions. For the first region (at small stimulus intensities) the FP duration was maximal and independent on the stimulus intensities. The second region began at the point where FP duration reduced presumably due to the feed-forward inhibition. The conditioning stimulus caused a widening (recovery) of the FP due to suppression of the inhibition. In the third region the stimulus intensity was sufficient to excite pyramidal cells and therefore to activate the feed-back inhibition. The time course of the FP was contaminated by the population spike and FP duration became inadequate for the evaluation of the "priming" effect. The second set of the experiments was aimed to study possible changes in the feed-back inhibition. With this end in view the influence of the conditioning (priming) procedure on the paired-pulse depression was studied. The main effect of the conditioning was a suppression of the paired-pulse depression, i.e. a suppression of the feed-back inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Event-related potential P300 in cerebral infarction

N1, P2 and P300 potentials were studied in 20 cases of cerebral infarction and 47 healthy controls with standard technique of auditory event-related potentials. Healthy controls of both sexes, different ages, education levels and cognitive capacity did not show apparent differences in the latency of p300 (P greater than 0.05, respectively). The patient group, however, revealed significant (P less than 0.001) prolongation of latency of P300 (mean = 409.6 +/- 50 ms) as compared with 28 well matched healthy subjects (mean = 337.7 +/- 24 ms). Although there was some decline of amplitude of P300 in the patient group, the difference between the control and patient groups was not significant (P greater than 0.05). There was significant difference in the Cognitive Capacity Screening Examination findings between the control and patient groups (P less than 0.01), but it seemed that the evaluation of latency of cognition-related p300 might be more objective and sensitive (P less than 0.001).     

PKC activation rescues LTP from NMDA receptor blockade

It has been proposed that a critical step in long-term potentiation (LTP) expression is the activation of presynaptic protein kinase C (PKC) after activation of postsynaptic NMDA receptors. A prediction from this "synaptic dialogue" hypothesis (Routtenberg, Trends Neurosci 1999;22:255-256) is that the well-known blockade of LTP by NMDA receptor antagonists would be rescued by direct activation of PKC. To test this prediction we recorded extracellular EPSPs in the molecular layer of the dentate gyrus (DG) in the intact, anesthetized mouse after stimulation of the perforant path. Three experimental series were performed in which tetanization was applied after continuous infusion of 1) vehicle, 2) NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (APV) (2.5+/-1.0 nmol), or 3) both APV and then PKC activator 4-beta-phorbol-12,13-dibutyrate (PDBu, 9.0+/-1.0 pmol). LTP was reliably induced in the first series (124+/-5%, N = 6; 2.5 h after the tetanus), suppressed by APV in the second series (95+/-18%, N = 4), and restored in the third series (121+/-13%, N = 5). Decreased paired-pulse facilitation, an index of presynaptic involvement in LTP expression, was observed after tetanization in the first and third series, but not in the second series. Blockade of LTP by NMDA receptor antagonists that can be overridden by presynaptic activation of PKC is thus consistent with the proposed hypothesis. As LTP is rescued after NMDA receptor blockade in transgenic mice overexpressing growth-associated presynaptic protein GAP-43, we suppose that this protein is one of the presynaptic targets of PKC activation.     

Somatosympathetic reflex in a working heart-brainstem preparation of the rat

The purpose of the present study was to examine the cardiorespiratory responses (CR) evoked by a somatosympathetic reflex (SSR) in the working heart-brainstem preparation (WHBP). Sprague-Dawley rats (75-100 g) were anesthetized with halothane, bisected sub-diaphramatically and decerebrated pre-collicularly (n = 15). The preparation was transferred to a recording chamber and perfused via the thoracic aorta with Ringer's solution containing an oncotic agent (Ficoll, 1.25%). SSR was activated by electrical stimulation (5 s) of the brachial nerve (0.5-40 Hz, 1-20 V, 0.1 ms) or the forelimb (0.5-40 Hz, 5-60 V, 2 ms). Stimulation at 40 Hz significantly increased heart rate (HR, 366 +/- 10 to 374 +/- 9 beats/min), systemic perfusion pressure (PP, 83 +/- 5 to 89 +/- 6 mmHg) and phrenic nerve discharge (PND, 0.4 +/- 0.1 to 1.4 +/- 0.3 Hz). Ganglionic blockade with hexamethonium (300 microM) eliminated the tachycardia and pressor response but did not alter the tachypnea to forelimb stimulation (n = 3). Transection of the brachial nerve plexus abolished the increase in PP and PND (n = 4). This indicates that a neural reflex mediated these responses. Spinal transection (C1-C2) completely abolished all responses indicating that they were mediated via a supraspinal pathway (n = 2). Based upon these findings, we conclude that activation of somatosensory afferent fibers in the WHBP evokes a programmed pattern of autonomic responses altering the activity-state of both the cardiovascular and respiratory systems. The WHBP provides a unique opportunity to investigate the medullary circuits and neuronal mechanisms that may be involved in coupling cardiorespiratory and somatomotor activity during locomotion/exercise.     

Donepezil versus vitamin E in Alzheimer's disease: Part 2: mild versus moderate-severe Alzheimer's disease

SUMMARY: Early studies showed that the latency of P300 (P3) event related potential increases or diminishes when anticholinergic or cholinergic drugs are administered. We tested the hypothesis that new cholinesterase inhibitors like Donepezil (DPZ) may have an effect on the often abnormal P300 of patients with Alzheimer's Disease (AD), and therefore, that P300 recordings might simplify the evaluation of responses to cholinesterase inhibitor in patients with mild and moderate-severe AD. We evaluated 60 patients with AD: 30 patients with "mild" (Mini Mental State Examination 26-19) and 30 patients with "moderate-severe" (Mini Mental State Examination 18-10), according to the National Institute of Neurological and Communicative Disorders and Alzheimer's Disease and Related Disorders Association criteria in comparison with 40 age-matched controls. All subjects underwent P300 recordings and neuropsychologic examinations (Alzheimer's Disease Assessment Scale-Cognition and Wechsler Adult Intelligence Scale) during the 6-month follow-up. Patients were divided into four groups of 15 patients each: Group I DPZ (10 mg/day) and Group I Vitamin E (2000 IU/day) with "mild" AD; Group II DPZ and Group II Vitamin E with "moderate-severe" AD and same drug dosages. In patients treated with Vitamin E, we observed P3 latency increments (delta) by 11.8 +/- 1.8 ms in Group I and by 12.8 +/- 2.8 ms in Group II at 6 months; neuropsychologic test scores significantly worsened at 6 months (p < 0.001) in Group II patients. Donepezil induced significant P3 latency reductions (11.2 +/- 2.4 ms) in nine patients of Group I and all patients of Group II (16.1 +/- 4.0 ms), reaching a maximum at 3 months (23.2 +/- 2.7 ms). Alzheimer's Disease Assessment Scale-Cognition and Wechsler Adult Intelligence Scale scores improved during the same period, and the difference between Vitamin E and DPZ treated patients was highly significant for P3 (analysis of variance) and for P3-Alzheimer's Diseases Assessment Scale-Cognition (analysis of covariance) with p < 0.001 for pooled groups of patients with AD and Group II (DPZ) versus Group II (Vitamin E). Combined P3 event related potentials measurements, neuropsychologic test comparison evidences significant effects of DPZ in mild and in moderate-severe AD.     

Heart rate and arterial pressure variability in the experimental renovascular hypertension model in rats

This study was conducted in one kidney, one clip (1K1C) Goldblatt hypertensive rats to evaluate vascular and cardiac autonomic control using different approaches: 1) evaluation of the autonomic modulation of heart rate (HR) and systolic arterial pressure (SAP) by means of autoregressive power spectral analysis 2) assessment of the cardiac baroreflex sensitivity; and 3) double blockade with methylatropine and propranolol. The 1K1C group developed hypertension and tachycardia. The 1K1C group also presented reduction in variance as well as in LF (0.23+/-0.1 vs. 1.32+/-0.2 ms2) and HF (6.6+/-0.49 vs. 15.1+/-0.61 ms2) oscillations of pulse interval. Autoregressive spectral analysis of SAP showed that 1K1C rats had an increase in variance and LF band (13.3+/-2.7 vs. 7.4+/-1.01 mmHg2) in comparison with the sham group. The baroreflex gain was attenuated in the hypertensive 1K1C (-1.83+/-0.05 bpm/mmHg) rats in comparison with normotensive sham (-3.23+/-0.06 bpm/mmHg) rats. The autonomic blockade caused an increase in the intrinsic HR and sympathetic predominance on the basal HR of 1K1C rats. Overall, these data indicate that the tachycardia observed in the 1K1C group may be attributed to intrinsic cardiac mechanisms (increased intrinsic heart rate) and to a shift in the sympathovagal balance towards cardiac sympathetic over-activity and vagal suppression associated to depressed baroreflex sensitivity. Finally, the increase in the LF components of SAP also suggests an increase in sympathetic activity to peripheral vessels.     

Low level of intracortical inhibition in children shown by transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to evaluate the integrity and maturation of the corticospinal tract. TMS was used in this study to compare intracortical inhibition (ICI) in children, adolescents, and adults. The paired-pulse technique of TMS with interstimulus intervals of 2 ms was used to determine the ratio of conditioned (cMEP) and unconditioned amplitudes (ucMEP) that measures ICI. In experiment 1 (Exp 1) stimulus intensity was adapted to motor threshold (50 healthy subjects; 24 male, 26 female, median age 13.5 years, range 6.3 - 34 years) and in experiment 2 (Exp 2) stimulus intensity was adapted to the ucMEP (200 - 400 microV). Children (quotient of cMEP and ucMEP: Exp. 1: 0.71 +/- 0.41, Exp. 2: 0.82 +/- 0.25) had significantly less ICI compared to adults (Exp. 1: 0.21 +/- 0.19, mean +/- STD, Exp. 2: 0.35 +/- 0.22, in both experiments p < 0.001). Recently, ICI has been linked to the regulating function of GABAergic cortical interneurons on practice-dependent neuronal plasticity. Therefore, the lower ICI in children points to maturation processes that may have implications for the greater capacity of practice-dependent neuronal plasticity in children.     

The metabotropic glutamate receptor 5 is necessary for late-phase long-term potentiation in the hippocampal CA1 region

Selective antagonists of the metabotropic receptors 1 (mGluR1), +/-2-methyl-4-carboxyphenylglycine (LY367385), and mGluR5, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), were used to investigate the role of group I metabotropic receptors in late-phase long-term potentiation (L-LTP) at Schaffer collateral/commissural fiber-CA1 synapses in rat hippocampal slices. L-LTP was induced with three trains of tetanization of 1 s duration at 100 Hz separated by 10-min intervals. Neither LY367385 nor MPEP affected basal synaptic responses at the doses used (200 and 10 microM, respectively) and only the mGluR5 inhibitor MPEP blocked L-LTP. However, in agreement with previous mouse mutant studies, we found that both LY367385 and MPEP inhibited the induction of an LTP obtained with a single train of tetanization of 1 s duration at 100 Hz. MPEP's ability to disrupt L-LTP was not due to an effect on NMDA responses since it did not affect pharmacologically isolated N-methyl-D-aspartate (NMDA) excitatory postsynaptic potentials (EPSPs). However, MPEP prevented the increased phosphorylation in dendrites of p70 S6 kinase (p70(S6K)) at Thr3889, a major regulator of translation required for the induction of protein synthesis-dependent forms of LTP.