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PubMed1998

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.

2-Amino-5-phosphonovalerate↗
PubMed1996

Dopamine reverses the depression of rat corticostriatal synapses which normally follows high-frequency stimulation of cortex in vitro.

Learning deficits resulting from dopamine depletion suggest that striatal dopamine release is crucial for reinforcement. Recently described firing patterns of dopamine neurons in behaving monkeys show that transient increases in dopamine release are brought about by reinforcement. We describe an enduring change in the strength of synaptic transmission following pulsatile application of dopamine intended to mimic the transient increases associated with reinforcement. Intracellular records were made from neurons in slices of the rat corticostriatal system. Neurons having the properties of the medium-sized spiny neurons responded to cortical stimulation with depolarizing potentials (peak amplitude 12.0 +/- 1.3 mV; latency 9.2 +/- 0.1 ms; mean +/- S.D., n = 19), which had the properties of monosynaptic excitatory postsynaptic potentials. After trains of stimuli to the cortex had been applied in conjunction with intracellular depolarizing current, the size of these excitatory postsynaptic potentials was reduced (-27% at 20 min). Application of dopamine (approximately 30 microM) in a solution containing KCl concomitant with depolarization and presynaptic activation increased the subsequent excitatory postsynaptic potentials (+21% at 20 min) without significant lasting change in the membrane properties of the postsynaptic cell. This suggests that dopamine has an enduring, activity-dependent action on the efficacy of corticostriatal transmission, which may be a cellular basis for the learning-related effects of the nigrostriatal system.

Animals↗
PubMed1986

Associative induction of posttetanic and long-term potentiation in CA1 neurons of rat hippocampus.

Electrical stimulation of fibers in the stratum radiatum causes an excitatory postsynaptic potential in CA1 neurons of the hippocampus. Other excitatory inputs to or direct depolarization of these CA1 neurons during stimulation of the stratum radiatum caused a subsequent increase in the excitatory postsynaptic potential. This enhancement was characterized as a brief potentiation (2 to 3 minutes, similar to posttetanic potentiation) and a long-term potentiation (presumed to be involved in learning and memory). These potentiations are probably induced by an interaction of the postsynaptic cell or other presynaptic terminals with the test presynaptic terminals.

Action Potentials↗
PubMed1997

Patterns of inputs to the parietal cortex efferent neurons from the motor cortex and cerebellum in the cat.

Responses of parietal association cortex efferent neurons to motor cortex and cerebellar nuclei stimulation were studied intracellularly in anaesthetized cats. Efferent neurons of the parietal cortex were identified according to their antidromic activation on stimulation of the motor cortex, pontine nuclei proper and red nucleus. Monosynaptic excitatory postsynaptic potentials of ipsilateral anterior suprasylvian and lateral gyri neurons to motor cortex stimulation have been established. Oligo- and polysynaptic excitatory responses of parietal cortex efferent neurons to cerebellar nuclei stimulation have been recorded. Correlation between the latencies of cerebellar-induced excitatory postsynaptic potentials and antidromic invasion of neurons on stimulation of different parietal cortex efferent projections (corticocortical, corticopontine, corticorubral) has been obtained. A similar correlation has been found between the latencies of excitatory postsynaptic potentials evoked on stimulation of one of the cerebellar nuclei and latencies of antidromic invasion induced on stimulation of all studied parietal cortex efferent systems. Feedforward and feedback mechanisms in the input-output organization of parietal association cortex have been discussed.

Animals↗
PubMed1983

Mechanisms regulating the activity of facial nucleus motoneurones--2. Synaptic activation from the caudal trigeminal nucleus.

Field and postsynaptic potentials of facial motoneurones evoked by stimulation of the caudal trigeminal nucleus were studied in cats by means of extra- and intracellular recording. Mono- and polysynaptic input onto facial motoneurones from the caudal trigeminal nucleus were shown. Four types of responses were distinguished: excitatory postsynaptic potentials generating a single action potential; a gradual shift of depolarization inducing multiple discharges; a rhythmic discharge of action potentials appearing at a low level of depolarization; excitatory postsynaptic potentials or a sequence of excitatory and inhibitory postsynaptic potentials. Multiple discharge was shown to appear as a result of effective summation of high frequency excitatory influences from efferent neurones of the caudal trigeminal nucleus projecting into the facial nucleus. Factors facilitating the development of gradual depolarization are: dendritic localization of synaptic terminals, dendritic origin of after-depolarizing processes and the high input resistance of the facial motoneurone membrane. It is thought that specific features of facial motoneurones and properties of afferent inputs are supposed to provide high sensitivity of neuronal organization of the facial nucleus to afferent signals as well as wide diversity in controlling its activity.

Animals↗
PubMed1995

Increases in non-N-methyl-D-aspartate glutamatergic transmission, but no change in gamma-aminobutyric acidB transmission, in CA1 neurons during withdrawal from in vivo chronic ethanol treatment.

Evoked fast excitatory postsynaptic potentials and slow inhibitory postsynaptic potentials were measured in mouse CA1 neurons in hippocampal slices after chronic ethanol treatment in vivo. Intracellular recordings were made 2, 4 and 6 hr after ethanol withdrawal, i.e., after the beginning of slice preparation. The resting membrane potentials were standardized to -60 mV by using constant current injection. The fast excitatory postsynaptic potentials were isolated by adding DL-2-amino-5-phosphonopentanoic acid, bicuculline and nitrendipine to the bathing solution and injecting QX-314 into the recording cell; stimulation then evoked a monophasic depolarization with a maximum of 16.3 mV at about 30 msec after stimulation, which was inhibited by 6-cyano-7-nitroquinozaline-2,3-dione. At 4 and 6 hr after withdrawal, but not at 2 hr, the estimated fast excitatory postsynaptic potential conductance in slices from ethanol-treated mice was significantly larger than in those from control animals. There were no changes in stimulus/response relation or voltage-dependency of the depolarization. In the presence of these blocking agents, the thresholds for elicitation of field potentials was decreased at 6 hr from withdrawal. The slow inhibitory postsynaptic potentials were isolated by adding DL-2-amino-5-phosphonopentanoic acid, 6-cyano-7-nitroquinozaline- 2,3-dione and bicuculline to the bathing solution; stimulation of the Schaffer collateral fibers then evoked a monophasic hyperpolarization with a maximum of 5.7 mV at about 180 msec after stimulation, which was inhibited by the gamma-aminobutyric acidB antagonist saclofen. At the three time points, the stimulus/response relation, voltage dependency of the hyperpolarization and estimated slow inhibitory postsynaptic conductance in ethanol-treated mice did not differ from control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Correlation of electrophysiological and morphological characteristics of enteric neurons in the mouse colon.

We report on the first correlative study of the electrophysiological properties, shapes, and projections of enteric neurons in the mouse. Neurons in the myenteric plexus of the mouse colon were impaled with microelectrodes containing biocytin, their passive and active electrophysiological properties determined, and their responses to activation of synaptic inputs investigated. Biocytin, injected into the neurons from which recordings were made, was converted to an optically dense product and used to determine the shapes of neurons. By electrophysiological properties, almost all neurons belonged to one of two classes, AH neurons or S neurons. AH neurons had a biphasic repolarization of the action potential, and slow afterhyperpolarizing potentials usually followed the action potentials. S neurons had monophasic repolarizations, no slow afterhyperpolarization, and fast excitatory postsynaptic potentials in response to fibre tract stimulation. By shape, neurons were divided into Dogiel type II (28/136 neurons) and uniaxonal neurons. Dogiel type II neurons had large, smooth-surfaced cell bodies and several long processes that supplied branches within myenteric ganglia. All Dogiel type II neurons had AH electrophysiology; conversely, most AH neurons had Dogiel type II morphology. The majority of uniaxonal neurons had lamellar dendrites, i.e., Dogiel type I morphology. They projected to the circular muscle (circular muscle motor neurons), to the longitudinal muscle (longitudinal muscle motor neurons), and to other myenteric ganglia (interneurons) and in some cases could not be traced to target cells. All S neurons were uniaxonal. A small proportion of uniaxonal neurons (3/70) had AH electrophysiology. Fast excitatory synaptic potentials were only recorded from uniaxonal neurons and were in most cases blocked by nicotinic receptor antagonists. A small component of fast excitatory transmission in some neurons was antagonized by the purine receptor antagonist PPADS. Slow excitatory postsynaptic potentials were observed in both AH and S neurons. Slow inhibitory postsynaptic potentials were recorded from S neurons. We conclude that the major classes of neurons are Dogiel type II neurons with AH electrophysiological properties and Dogiel type I neurons with S electrophysiological properties. The S/Dogiel type I neurons include circular muscle motor neurons, longitudinal muscle motor neurons, and interneurons.

Action Potentials↗
PubMed1984

Somatic and dendritic actions of gamma-aminobutyric acid agonists and uptake blockers in the hippocampus in vivo.

In rats under urethane anaesthesia gamma-aminobutyric acid agonists and uptake blockers were microiontophoretically applied in the pyramidal layer of CA1 and in the apical dendrites using a twin set of multibarrelled micropipettes. Thus, the somatic and dendritic field potentials elicited by commissural stimulation were recorded simultaneously and the effects of iontophoretic applications at either site studied. Somatic applications of gamma-aminobutyric acid, isoguvacine or muscimol produced an inhibition of the somatic population spike; this showed rapid fade and was followed by an "off" response i.e. an enhancement of the population spike discharge and the occurrence of a second (and occasionally third) spike. The order of potency with regard to the "off" response was muscimol greater than isoguvacine much greater than gamma-aminobutyric acid. In contrast, the inhibition of the population spike produced by 4,5,6,7-tetrahydroisoxazolo(5,4-C) pyridin 3-OL showed little fade and no prominent "off" response. The fade and "off" response were not associated with significant changes in the dendritic field excitatory postsynaptic potential concommittantly recorded and were exclusively restricted to the immediate vicinity of the pyramidal layer. Ejection of gamma-aminobutyric acid and its agonists in the stratum radiatum produced a reduction of the field excitatory postsynaptic potential and the somatic spike, this effect however showed no fade (even during prolonged applications of high doses) and no "off" response. Somatic applications of the uptake blockers nipecotic acid or guvacine consistently produced: an increase in the effectiveness of the inhibition produced by gamma-aminobutyric acid and its analogues: a decrease in the latency to peak of the inhibition and an increase in the time to recovery; a full blockade of the fade and the "off" response. All of these effects were rapid and fully reversible without significant changes in either the field excitatory postsynaptic potential or the (control) somatic spikes. The more specific glial uptake blocker, 4,5,6,7-tetrahydroisoxazolo(4,5-C) pyridin 3-OL occasionally blocked the "off" response, however it was less potent and also tended to reduce the spike amplitude. Dendritic applications of the uptake blockers reduced the excitatory postsynaptic potential and the somatic spike but failed to produce prominent changes in the action of gamma-aminobutyric acid and its analogues.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1999

Characteristics of mucosally projecting myenteric neurones in the guinea-pig proximal colon.

1. Using retrograde tracing with 1,1'-didodecyl-3,3,3', 3'-tetramethylindocarbocyanine perchlorate (DiI) in combination with electrophysiological and immunohistochemical techniques we determined the properties of the putative intrinsic primary afferent myenteric neurones with mucosal projections in the guinea-pig proximal colon. 2. Eighty-four out of eighty-five DiI-labelled myenteric neurones were AH neurones with a late after-hyperpolarization. Thirty-three per cent of them exhibited atropine- and tetrodotoxin-resistant spontaneously occurring hyperpolarizing potentials (SHPs) during which the membrane resistance and excitability decreased. 3. DiI-labelled AH neurones had multipolar Dogiel type II morphology, primarily of the dendritic type. Sixty-one per cent of the neurones were immunoreactive for choline acetyltransferase (ChAT) and calbindin (Calb) and 23 % were ChAT positive but Calb negative. 4. DiI-labelled neurones did not receive fast excitatory postsynaptic potentials but 94 % (34/36) received slow excitatory postsynaptic potentials (sEPSPs). The neurokinin-3 (NK-3) agonist (MePhe7)-NKB but not the NK-1 agonist [(SAR9,Met(O2)11]-SP mimicked this response. The NK-3 receptor antagonist SR 142801 (1 microM) significantly decreased the amplitude and duration of the sEPSPs; the NK-1 receptor antagonist CP-99,994 (1 microM) was ineffective. Atropine (0.5 microM) increased the duration but not the amplitude of the sEPSPs. 5. Microejection of 100 mM sodium butyrate onto the neurones induced in 90 % of the DiI-labelled neurones a transient depolarization associated with an increased excitability. In neurones with SHPs sodium butyrate evoked, additionally, a late onset hyperpolarization. Perfusion of 0.1-10 mM sodium butyrate induced a dose-dependent increase in neuronal excitability. Sodium butyrate was ineffective when applied directly onto the mucosa. 6. Mucosally projecting myenteric neurones of the colon are multipolar AH neurones with NK-3-mediated slow EPSPs and somal butyrate sensitivity.

Animals↗
PubMed1992

Alterations in the properties of hippocampal pyramidal neurons in the aged rat.

The electrophysiological and pharmacological properties of CA1 hippocampal pyramidal neurons were studied in slices from young (three to four months) and aged (25-32 months) Sprague-Dawley rats having previously performed two behavioral tasks. About 20% of the aged rats were impaired in either the spontaneous alternation task or the water maze task. Electrophysiological parameters were measured and compared in young and aged animals using intracellular recordings. No age-related differences were observed in membrane potential, input resistance, amplitude of action potentials or amplitude of calcium spikes. The amplitude and duration of individual afterhyperpolarizations following a single spike were unchanged. In contrast, the neuronal excitability was significantly decreased and the spike duration significantly enhanced in aged rats as compared to young rats. The comparison of afterhyperpolarizations (which follow a burst of spikes) between young and aged rats was more complex. An increase in the amplitude and duration of afterhyperpolarizations generally occurred in aged animals. However, this increase was not consistent among animals and was dependent on the holding potential of the neuron and on the number of action potentials used to trigger the afterhyperpolarization. The depolarizing effect of bath-applied carbachol, as well as the associated increase in membrane resistance were reduced in neurons from aged rats. In contrast, the effects of carbachol on the depression of synaptic events and the blockade of the afterhyperpolarizations were similar in young and aged animals. In addition, the amplitude of the slow cholinergic excitatory postsynaptic potential induced by stimulation of cholinergic afferents in the presence of physostigmine was also decreased in aged rats. Excitatory postsynaptic potentials and inhibitory postsynaptic potentials following electrical stimulation of stratum radiatum were compared. The amplitude and duration of excitatory postsynaptic potentials were increased in aged rats. The amplitude and duration of the fast inhibitory postsynaptic potential were not significantly affected in aged animals. In contrast, the duration of the slow inhibitory postsynaptic potential was decreased in aged rats. Since the mean baclofen-induced hyperpolarization was only slightly reduced in aged rats, the most likely explanation is a decrease in the release of GABA rather than an alteration in the postsynaptic response mediated by GABAB receptors. A statistically significant correlation was found between the degree of impairment in the spontaneous alternation task and the amplitude of the carbachol-induced depolarization.

Acetylcholine↗
PubMed1998

Electrophysiology, shape, and chemistry of neurons that project from guinea pig colon to inferior mesenteric ganglia.

BACKGROUND & AIMS: Prevertebral sympathetic ganglia receive inputs from intestinofugal neurons, with cell bodies located in the wall of the bowel. Intestinofugal neurons are part of the afferent limbs of intestino-intestinal reflexes. The aim of this study was to define the properties of intestinofugal neurons using intracellular recordings. METHODS: Intestinofugal neurons of the distal colon were retrogradely labeled from the inferior mesenteric ganglia. In whole mounts of the myenteric plexus/longitudinal muscle of the distal colon, labeled neurons were identified by their fluorescence and recordings were made using biocytin-filled electrodes. Labeled nerves were characterized immunohistochemically and morphologically. RESULTS: Intestinofugal neurons were uniaxonal neurons with multiple dendrites that had lamellar expansions. They were immunoreactive for choline acetyltransferase. Stimulation of nerve fiber tracts elicited large-amplitude excitatory postsynaptic potentials in all labeled neurons. Some received spontaneous fast excitatory postsynaptic potentials. Those cells that fired action potentials fired only one or two at the start of a depolarizing current pulse. No intestinofugal neurons had Dogiel type II morphology or a late afterhyperpolarizing potential. CONCLUSIONS: Intestinofugal neurons are likely to be activated by other neurons in the gut wall. They are not AH or Dogiel type II neurons. Thus they seem to be second order neurons in afferent pathways of intestino-intestinal reflexes.

Animals↗
PubMed2001

Identification of the source of the bilateral projection system from cortex to somatosensory neostriatum and an exploration of its physiological actions.

Microinjections of cholera toxin B subunit were made into the area of the neostriatum that receives input from the primary somatosensory barrel cortex (SI) in the rat. Studies of the cortices then allowed retrograde identification of the cortical cells supplying the striatal input. When injections were restricted to the neostriatum, retrograde labelling was found in layer V of both SI cortices. Ipsilateral to the injection, cells were retrogradely filled with toxin in all parts of the barrel field, in adjacent parietal cortex, in the motor cortex and in prefrontal areas. A similar distribution across cortical areas was seen contralaterally; however, the stained cells in the SI were between rather than within barrel columns. An earlier anterograde study suggested two inputs from the SI to the neostriatum. The present results indicate that one input to the somatosensory area of the neostriatum arises bilaterally from neurons between the barrels of the SI, while the topographic pathway from below the barrels is present only ipsilaterally. These anatomical results indicate that separate stimulation of the two corticostriatal pathways from the barrel cortex is possible. Electrical stimulation of the contralateral cortex will activate the bilateral pathway, while electrical stimulation of the whisker pads activates the barrels and hence the topographic pathway. Neurons in the somatosensory region of the striatum responded to stimuli in the contralateral cortex and in the contralateral whisker pad. In spite of very different path lengths, stimuli via the two routes gave rise to excitatory postsynaptic potentials in the striatal cells with similar latencies. The excitatory postsynaptic potentials to whisker pad stimulation had a rapid rise time and usually resulted in at least one action potential. Responses to stimulation of the contralateral cortex rose to a peak more slowly and were more variable in latency, but also gave rise to an action potential in the majority of cases. All the neurons had the physiological characteristics of medium-sized densely spiny cells and after intracellular filling with biocytin had the appropriate morphology. In summary, we propose that two corticostriatal pathways arise from layer V cells in the barrel area of the somatosensory cortex; one is bilateral and arises from cells mainly below the septa, while a topographical pathway arises from cells below the barrels. Both pathways can raise the spiny output cells of the striatum to firing threshold. The latencies from the contralateral cortex imply slowly conducting fibres with considerably more temporal dispersion than the pathway from below the barrels, which we excited from the contralateral periphery.

Animals↗
PubMed1984

Mu opioid receptors participate in the excitatory effect of opiates in the hippocampal slice.

The effects of the opioid peptides morphiceptin and [N-MePhe3-D-Pro4]morphiceptin (PL017), both mu receptor agonists, were examined by electrophysiological techniques in the rat hippocampal slice and ligand binding techniques in hippocampal membrane preparations. The electrophysiological actions of the mu agonists were similar to those of the previously studied delta receptor agonist [D-Ala2, D-Leu5]enkephalin. Thus, for a given size field excitatory postsynaptic potential the amplitude of both population spike and intracellular excitatory postsynaptic potential was increased by morphiceptin. These effects were concentration dependent and reversed by naloxone. The EC50 for morphiceptin was 1.6 microM, which is consistent with the mu-selective binding properties of this peptide. Similar results were obtained with the more potent analog PL017. Morphiceptin and morphine had similar displacement profiles in competition experiments performed with hippocampal membranes and a variety of radioligands. In Tris buffer morphiceptin potently inhibited the binding of the mu receptor marker [125I]FK 33,824 but displayed the expected shallow displacement isotherm against binding of the delta receptor marker [125I][D-Ala2, D-Leu5]enkephalin. A significant interaction of either morphiceptin or morphine with kappa binding sites is improbable since neither agonist could fully displace binding of [3H]ethylketocyclazocine or [3H]diprenorphine. The potency of morphiceptin in displacing [3H]naloxone from mu binding sites was reduced by inclusion of 100 mM NaCl or 100 microM GTP in the assay. The dissociation constant of morphiceptin for mu binding sites in physiological saline was 0.78 microM, comparable to its EC50 determined in electrophysiological experiments. It appears, therefore, that the electrophysiological properties of opioid peptides in the hippocampal slice may be mediated by both mu and delta receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed2000

Patch clamp studies of motor neurons in spinal cord slices: a tool for high-resolution analysis of drug actions.

AIM: To develop a tool for detailed analysis of spinally acting anesthetic and analgesic agents. METHODS: Studies were done on visually identified motor neurons in 400 microns thick spinal cord slices from 14-23 d old rats using patch clamp techniques. Ethanol was used as a prototype general anesthetic agent. RESULTS: Cell bodies in the ventrolateral horn identified as motor neurons by retrograde fluorescent labeling had a mean dimension of 32 +/- 5 microns (x +/- s, n = 25). Mean resting potential was -62.8 +/- 2.4 mV; input resistance was 44 +/- 24 M omega (n = 19). Threshold was -44 +/- 7 mV, and action potential amplitude 101 +/- 9 mV from baseline. Ethanol concentrations at and below 50-200 mmol/L decreased motor neuron excitability to the injected current; there was no effect on resting potential, but a variable reversible increase in input resistance. Ethanol reversibly depressed the excitatory postsynaptic potential, with a dose-response relationship similar to that previously observed for the population excitatory postsynaptic potential in intact spinal cord in vitro. Ethanol also reversibly depressed currents evoked by glutamate, reducing total charge transfer to 40% +/- 26% of control (x +/- s; n = 4). CONCLUSION: Reduction of connectivity in this relatively thick slice preparation does not significantly modify drug actions. The actions of ethanol on excitatory synaptic transmission observed in intact spinal cord are in part due to postsynaptic effects on motor neurons.

Anesthetics, General↗
PubMed2003

Novel modulatory mechanisms revealed by the sustained application of nicotine in the guinea-pig hippocampus in vitro.

The alpha 7 nicotinic acetylcholine receptor (nAChR) has been implicated widely in behavioural functions and dysfunctions related to the hippocampus, but the detailed mechanisms by which this receptor contributes to these behavioural processes have yet to be elucidated. In the present study, sustained application (5 min) of nicotine significantly lowered the threshold for synaptic plasticity, and thus a long-lasting potentiation was induced by a stimulus that would normally evoke only a short-term potentiation. This effect appeared to be mediated by alpha 7 nAChRs, as it was inhibited by the alpha 7 nAChR-specific antagonist alpha-bungarotoxin (100 nM), but not by mecamylamine (50 microM) or dihydro-beta-erythroidine (DH beta E; 1 microM) at concentrations known to be selective for non-alpha 7 nAChRs. Further pharmacological dissection revealed that the effect was also abolished by the NMDA receptor antagonist, D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 50 microM). This blockade, however, unmasked a slowly developing nicotine-induced potentiation of field excitatory postsynaptic potential that appeared to be dependent on both alpha 7 nAChR activation and non-alpha 7 nAChR desensitisation. This secondary effect of nicotine was blocked by a combination of picrotoxin (50 microM) and saclofen (100 microM), and thus appeared to be mediated via GABAergic interneurons. The important implication of this study was that the sustained application of alpha 7 nAChR agonists could modulate the conditions for synaptic plasticity through multiple transduction pathways, and not simply the inactivation of alpha 7 nAChRs. These alpha 7-nAChR-dependent mechanisms could reconcile the discrepancies between the previously reported behavioural versus electrophysiological effects of nicotine in the hippocampus. Effects of sustained alpha 7 nAChR stimulation Effects of sustained alpha 7 nAChR stimulation Effects of sustained alpha 7 nAChR stimulation Effects of sustained alpha 7 nAChR stimulation Effects of sustained alpha 7 nAChR stimulation

2-Amino-5-phosphonovalerate↗
PubMed2003

Low-frequency depression of synaptic responses recorded from rat visual cortex.

To characterize the low-frequency depression (LFD) of synaptic transmission in the visual cortex, we recorded field potentials and minimal excitatory postsynaptic potentials (EPSPs) from layer II/III following intracortical stimulation at various frequencies in cortical slices of rats. Field potentials were stable at 0.017 Hz, but showed an amplitude depression at 0.033-0.1 Hz at stimulus intensity of 1.5 times the threshold for induction of the postsynaptic component and at 0.1-0.2 Hz at intensity of 1.2 times the threshold. The LFD was input-specific and its magnitude correlated with the stimulus frequency. An interruption of stimulation for 15 min yielded a nearly complete recovery from LFD. Minimal EPSPs tested at 0.1-1.7 Hz often showed LFD with similar features. However, some inputs were stable or even facilitated during repeated stimulation. At 0.1 and 0.2 Hz, >50% of inputs were stable, whereas 10% and 25% were depressed, respectively. At 0.5 and 1.7 Hz, LFD was observed in >60% and 80% of inputs, respectively. The magnitude of LFD strongly varied across inputs. In 3 of the 41 inputs analyzed, LFD was so strong that these inputs became virtually silent. Occurrence of responses to the second pulse in the paired-pulse paradigm when the first response was absent and recovery of depressed EPSPs following stimulus interruption or shift to a lower frequency suggest that these synapses were presynaptically silent due to a lowered probability of transmitter release. Altogether, the results indicate that testing intervals of <10 or even < or =30 s cannot be regarded as completely neutral. At the single-cell level, frequency-dependent changes were strongly heterogeneous across different inputs. LFD and its spontaneous recovery may underlie the previously described "post-rest" potentiation, and should be taken into account when considering information processing in cortical networks.

Animals↗
PubMed1991

Neuropharmacology of the muscarinic antagonist telenzepine in myenteric ganglia of the guinea-pig small intestine.

Intracellular recording methods were used to investigate the actions of the putative M1 muscarinic receptor antagonist telenzepine on the electrical and synaptic behavior of myenteric neurons. Telenzepine had no effect on resting membrane potential, input resistance, excitability and antidromic potentials in both AH/type 2 and S/type 1 neurons, when applied in concentrations of 0.1-2000 nM, although higher concentrations (10-100 microM) did have a significant non-specific effect on the postsynaptic membrane. Micromolar concentrations of telenpzepine (1-2 microM) had no effect on excitatory responses to substance P, vasoactive intestinal peptide, the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium or the nicotinic action of acetylcholine. Nicotinic fast excitatory postsynaptic potentials were also unaffected by 2 microM telenzepine. In contrast, at submicromolar concentrations (100 nM), telenzepine abolished responses to either muscarine or the muscarinic component of the acetylcholine response. The excitatory effect of muscarine at postsynaptic M1 receptors was dose dependently inhibited by telenzepine (0.1-1000 nM) at concentrations which had no effect on the electrical properties of the cells. This effect was slowly reversible, usually requiring more than 60 min for significant recovery. The threshold dose of telenzepine as an antagonist of the muscarinic depolarization in AH/type 2 neurons was in the range of 0.1-1 nM. The IC50 concentration of telenzepine needed to abolish the response was 8.5 nM. A small proportion of stimulus-evoked slow excitatory postsynaptic potentials in both AH/type 2 and S/type 1 cells were abolished by 1 microM telenzepine, while the majority of them remained unaffected, indicating that some slow excitatory postsynaptic potentials are mediated by the muscarinic action of released acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

The effects of angiotensin IV analogs on long-term potentiation within the CA1 region of the hippocampus in vitro.

Within the brain-renin angiotensin system, it is generally assumed that angiotensin peptide fragments shorter than angiotensins II and III, including angiotensin IV (AngIV), are inactive. This belief has been challenged by the recent discovery that AngIV, and AngIV-like analogs, bind with high affinity and specificity to a putative angiotensin binding site termed AT4. In the brain these sites include the hippocampus, cerebellum, and cerebral cortex, and influence associative and spatial learning tasks. The present study investigated the effects of two AngIV analogs, Nle1-AngIV (an AT4 receptor agonist) and Nle1-Leual3-AngIV (an AT4 receptor antagonist), on long-term potentiation (LTP). Field excitatory postsynaptic potentials (fEPSPs) were recorded from the CA1 stratum radiatum following stimulation of the Schaffer collateral pathway. Activation of AT4 receptors by Nle1-AngIV enhanced synaptic transmission during low-frequency test pulses (0.1 Hz), and increased the level of tetanus-induced LTP by 63% over that measured under control conditions. Paired stimulation before and during infusion of Nle1-AngIV indicated no change in paired-pulse facilitation (PPF) as a result of AT4 receptor activation suggesting that the underlying mechanism(s) responsible for Nle1-AngIV-induced increase in synaptic transmission and LTP is likely a postsynaptic event. Further, applications of Nle1-Leual3-AngIV prior to, but not 15 or 30 min after, tetanization prevented stabilization of LTP. These results extend previous findings from behavioral data in that AT4 receptor agonists and antagonists are capable of activating, and inhibiting, learning and memory pathways in the hippocampus, and suggest that the AT4 receptor subtype is involved in synaptic plasticity.

Angiotensin II↗