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Results for “Long-Term Synaptic Depression”

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PubMed1991

Antidepressants affect amine modulation of neurotransmission in the rat hippocampal slice--I. Delayed effects.

The effects of long-term treatment with the antidepressant drugs, desipramine (DMI) and mianserin (MIA) on neurotransmission in the hippocampal slice were studied by examining the actions of serotonin (5-HT), isoprenaline and (+/-)-baclofen on the population spike in the pyramidal cell layer, recorded in area CA1. The decrease in amplitude of the population spike by 5-HT (1-10 microM) was facilitated by long-term treatment with DMI but not significantly with MIA. Both DMI and MIA depressed the excitatory action of isoprenaline (0.3 microM), whereas the inhibitory responses to (+/-)-baclofen (0.3-3 microM) were unaffected. The results show that significant changes in serotonergic and beta-adrenergic neurotransmission can be demonstrated ex vivo after in vivo treatment with antidepressants and that these changes partly substantiate data measured in vivo.

Adaptation, Physiological↗

PubMed1992

The synaptic activation of NMDA receptors and Ca2+ signalling in neurons.

Long-term potentiation (LTP) in the hippocampus is a model system for understanding the synaptic basis of learning and memory. We have studied the mechanism of induction of LTP using voltage-clamp techniques and confocal imaging of Ca2+ in rat hippocampal slices. In the Schaffer collateral-commissural pathway the neurotransmitter L-glutamate activates two classes of ionotropic receptor, named after the selective ligands AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) and NMDA (N-methyl-D-aspartate). During low frequency transmission the excitatory postsynaptic potential (EPSP) is mediated predominantly by AMPA receptors. NMDA receptors play a minor role because their ion channels are substantially blocked by Mg2+, and this block is intensified by GABA-mediated synaptic inhibition. During high frequency transmission the GABA-mediated inhibition is depressed, by mechanisms initiated by GABAB autoreceptors. This allows a greater contribution from the NMDA receptors, through which Ca2+ enters the dendrites of the postsynaptic neurons to initiate a cascade of biochemical processes which ultimately result in enhanced synaptic efficiency.

Animals↗

PubMed1991

GABA autoreceptors regulate the induction of LTP.

Understanding the mechanisms involved in long-term potentiation (LTP) should provide insights into the cellular and molecular basis of learning and memory in vertebrates. It has been established that in the CA1 region of the hippocampus the induction of LTP requires the transient activation of the N-methyl-D-aspartate (NMDA) receptor system. During low-frequency transmission, significant activation of this system is prevented by gamma-aminobutyric acid (GABA) mediated synaptic inhibition which hyperpolarizes neurons into a region where NMDA receptor-operated channels are substantially blocked by Mg2+ (refs. 5, 6). But during high-frequency transmission, mechanisms are evoked that provide sufficient depolarization of the postsynaptic membrane to reduce this block and thereby permit the induction of LTP. We now report that this critical depolarization is enabled because during high-frequency transmission GABA depresses its own release by an action on GABAB autoreceptors, which permits sufficient NMDA receptor activation for the induction of LTP. These findings demonstrate a role for GABAB receptors in synaptic plasticity.

2-Chloroadenosine↗

PubMed1991

Minimal stimulus parameters and the effects of hyperpolarization on the induction of long-term potentiation in the cat motor cortex.

The aim of the research program of which the present work is a part is to understand the neural mechanisms involved in motor learning and memory. One of the mechanisms postulated to be involved in this process is the induction of long-term potentiation (LTP) in the motor cortex. LTP can be induced in motor cortical neurons by tetanic stimulation of their afferents from the somatosensory cortex. In the present study, the effects of different stimulating parameters on the induction of LTP were examined, using in-vivo, intracellular recordings from anesthetized cats. The expression of LTP was documented by measuring the amplitude and rise-time of excitatory postsynaptic potentials (EPSPs) before and after tetanic stimulation. The minimal tetanic stimulation capable of systematically inducing LTP was found to consist of a train of stimuli at 50 Hz, 5 s. Shorter trains of stimulation produced only a short-lasting, transient potentiation. In different cells, identical stimulation parameters resulted in different degrees of potentiation of synaptic responses. Following all the stimulation trains examined, EPSP amplitudes were transiently depressed before reaching potentiated levels. The duration of this depression was directly correlated with the duration and the frequency of the tetanic stimulation. In all the cells in which LTP was induced, the variability in the amplitudes of potentiated EPSP was significantly greater than that of control EPSP amplitudes. Hyperpolarization of the postsynaptic cell, during the delivery of the tetanic stimulation, inhibited the induction of LTP. These phenomena are discussed in relation to the postulated mechanisms of LTP induction in the cortex.

Afferent Pathways↗

PubMed1991

Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine--I. Effects of acute and long-term administration of tandospirone on serotonin neurotransmission.

The acute and long-term effects of the antidepressant/anxiolytic selective 5-HT1A receptor ligand, tandospirone (SM-3997) on 5-HT neurotransmission were assessed using single-cell extracellular recording in chloral hydrate-anaesthetized rats. The acute intravenous administration of tandospirone decreased the firing rate of 5-HT neurones of the dorsal raphe (ED50 = 9.1 +/- 1.1 micrograms/kg). A treatment with tandospirone for 2 days (10 mg/kg/day, s.c.), markedly reduced the firing activity of 5-HT neurones of the dorsal raphe; this was followed by a partial recovery after 7 days and by complete recovery after 14 days of administration of tandospirone. After treatment with tandospirone for 14 days (10 mg/kg/day, s.c.), the responsiveness of 5-HT neurones to the intravenous administration of LSD was reduced, suggesting that somatodendritic 5-HT autoreceptors had desensitized. The depressant effects of microiontophoretically-applied tandospirone and 5-HT, on the firing activity of CA3 pyramidal neurones in the hippocampus were blocked by the intravenous injection of the 5-HT1A receptor antagonist, BMY-7378. The depressant effect of microiontophoretically-applied 5-HT onto these same neurones was markedly reduced during concurrent background application of tandospirone, suggesting that the latter acted as a partial agonist at postsynaptic 5-HT1A receptors. The sustained administration of tandospirone for 14 days (10 mg/kg/day, s.c.) altered neither the effectiveness of microiontophoretically-applied 5-HT and tandospirone nor that of endogenous 5-HT, released by the electrical simulation of the afferent 5-HT pathway, in suppressing the firing activity of pyramidal neurones in the hippocampus, suggesting that postsynaptic 5-HT1A receptors had not desensitized. Furthermore, long-term treatment with tandospirone did not alter the sensitivity of the terminal 5-HT autoreceptor. It is thus concluded that desensitization of somatodendritic 5-HT autoreceptors permits 5-HT neurones to regain their physiological rate of firing during long-term treatment with tandospirone and, consequently, to release a normal amount of 5-HT into the synaptic cleft. This, combined with the sustained activation of normosensitive postsynaptic 5-HT1A receptors by tandospirone, during such a treatment, should result in an enhanced tonic activation of postsynaptic 5-HT1A receptors.

Animals↗

PubMed1979

Chronic treatment with lithium or desipramine alters discharge frequency and norepinephrine responsiveness of cerebellar Purkinje cells.

Cerebellar Purkinje cells were studied by electrophysiological techniques in rats treated chronically with either desipramine (DMI) or lithium chloride given intragastrically. A striking decrement occurred in discharge frequencies of simple spikes and climbing fiber bursts in both groups of animals, similar to the depression produced by iontophoresis of these agents. Chronic treatment with DMI markedly decreased responsiveness to iontophoretically applied norepinephrine (NE), whereas long-term LiCl therapy slightly enhanced response to NE; responses to gamma-aminobutyric acid were unchanged by these treatments. The inhibitory responses to locus ceruleus stimulation were unaffected by chronic LiCl treatment. The effects of these chronic treatments on responsiveness to NE are opposite to the effects these same drugs produce when administered by acute iontophoresis to single cells: DMI then potentiates and LiCl antagonizes noradrenergic responses. These results provide electrophysiological evidence for reciprocal adaptive changes in NE sensitivity, supporting results of biochemical studies.

Animals↗

PubMed1990

Spatial overlap between populations of synapses determines the extent of their associative interaction during the induction of long-term potentiation and depression.

1. This study evaluates the associative interactions between inputs that lead to long-term potentiation (LTP) and long-term depression (LTD) in the dentate gyrus (DG). Previous studies have revealed that when two inputs are coconditioned, the extent of LTP is greater than when each input is conditioned alone. Moreover, for a weak input that does not show LTP when conditioned alone, LTP can be induced in that weak input if it is coconditioned with a strong input. LTD results when one input is silent when another is conditioned. In the present study, we evaluate whether these associative interactions depend on the extent of overlap of the terminal fields of the different inputs. 2. The experiment took advantage of the topographical organization of the temporodentate pathway from the entorhinal cortex (EC) to the DG. Four stimulating electrodes were placed so as to activate ipsilateral and crossed components of the projections from medial and lateral portions of the EC. Recording electrodes were positioned unilaterally in the DG so as to record field potentials. The localization of the synaptic field that was activated by each electrode was determined by current source density (CSD) analysis. The extent of overlap between the terminal fields of ipsi- and contralateral pathways was assessed, and the pathways were divided into groups where the overlap between current sinks was 0-50 or 51-100%. 3. Conditioning stimulation (400-Hz trains of 8 pulses delivered 8 times) was delivered to pathways alone or in combination with other pathways. The extent of LTP was evaluated after coactivation of pathways that overlapped substantially (51-100%) or minimally (0-50%). The extent of LTD was evaluated in pathways that were silent during conditioning of other overlapping or nonoverlapping pathways. 4. The extent of associative LTP or LTD depended on the extent of overlap between the terminal fields of pathways. Coactivation of two pathways that overlapped by 51-100% led to LTP; coactivation of pathways that overlapped by 0-50% did not. Moreover, LTD was induced in a crossed pathway when an ipsilateral pathway that overlapped by 51-100% was activated, but not when a nonoverlapping (0-50% overlap) ipsilateral pathway was activated. The degree of associative LTP or LTD that was induced in crossed pathways was correlated with the percent overlap with the terminal field of the active ipsilateral pathway. 5. Evaluation of whether LTD was induced when one division (medial or lateral) of the ipsilateral pathway was silent when the other division was conditioned revealed similar relationships.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Induction of long-term potentiation without participation of N-methyl-D-aspartate receptors in kitten visual cortex.

1. Intracellular recording was made from layer II-III cells in slice preparations of kitten (30-40 days old) visual cortex. Low-frequency (0.1 Hz) stimulation of white matter (WM) usually evoked an excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP). The postsynaptic potentials (PSPs) showed strong dependence on stimulus frequency. Early component of EPSP and IPSP evoked by weak stimulation both decreased monotonically at frequencies greater than 0.5-1 Hz. Strong stimulation similarly depressed the early EPSP at higher frequencies (greater than 2 Hz) and replaced the IPSP with a late EPSP, which had a maximum amplitude in the stimulus frequency range of 2-5 Hz. 2. Very weak WM stimulation sometimes evoked EPSPs in isolation from IPSPs. The falling phase of the EPSP revealed voltage dependence characteristic to the responses mediated by N-methyl-D-aspartate (NMDA) receptors and was depressed by application of an NMDA antagonist DL-2-amino-5-phosphonovalerate (APV), whereas the rising phase of the EPSP was insensitive to APV. 3. The early EPSPs followed by IPSPs were insensitive to APV but were replaced with a slow depolarizing potential by application of a non-NMDA antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX), indicating that the early EPSP is mediated by non-NMDA receptors. The slow depolarization was mediated by NMDA receptors because it was depressed by membrane hyperpolarization or addition of APV. 4. The late EPSP evoked by higher-frequency stimulation was abolished by APV, indicating that it is mediated by NMDA receptors, which are located either on the recorded cell or on presynaptic cells to the recorded cells. 5. Long-term potentiation (LTP) of EPSPs was examined in cells perfused with solutions containing 1 microM bicuculline methiodide (BIM), a gamma-aminobutyric acid (GABA) antagonist. WM was stimulated at 2 Hz for 15 min as a conditioning stimulus to induce LTP, and the resultant changes were tested by low-frequency (0.1 Hz) stimulation of WM. 6. LTP of early EPSPs occurred in more than one-half of the cells (8/13) after strong conditioning stimulation. The rising slope of the EPSP was increased 1.6 times on average. 7. To test involvement of NMDA receptors in the induction of LTP in the early EPSP, the effect of conditioning stimulation was studied in a solution containing 100 microM APV, which was sufficient to block completely synaptic transmission mediated by NMDA receptors. LTP occurred in the same frequency and magnitude as in control solution.

2-Amino-5-phosphonovalerate↗

PubMed1986

Modification of serotonergic and noradrenergic neurotransmissions by repeated administration of monoamine oxidase inhibitors: electrophysiological studies in the rat central nervous system.

The net effect of repeated administration of monoamine oxidase inhibitors (MAOI) on central serotonergic (5-HT) and noradrenergic (NE) neurotransmissions was studied by assessing the responsiveness of hippocampal pyramidal neurons to microiontophoretically applied 5-HT and NE and the response of these neurons to the electrical activation of the 5-HT and NE ascending pathways. Brain monoamine oxidase (MAO) activity as well as the levels of 5-HT, NE and their metabolites were determined in order to verify the biochemical effects of the drugs administered. Twenty-one-day treatments with clorgyline and deprenyl inhibited very selectively MAO-A and MAO-B, respectively, whereas a treatment with phenelzine inhibited both forms of the enzyme. Whole brain concentrations of 5-HT and NE were increased by the antidepressant drugs clorgyline and phenelzine whereas deprenyl, an MAOI type B ineffective in endogenous depression, increased only NE levels after a 21-day treatment. The responsiveness of hippocampal pyramidal neurons to 5-HT was decreased by the long-term clorgyline treatment, but not by deprenyl and phenelzine, whereas that to NE was not altered by any of the treatments. The suppression of firing of these same neurons induced by the stimulation of the 5-HT pathway was increased by clorgyline and phenelzine, but not by deprenyl. The effect of the stimulation of the dorsal NE bundle was not modified by any of the treatments. These data show that prolonged inhibition of MAO-A, but not that of MAO-B, results in an enhanced 5-HT neurotransmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1991

Inositol 1,4,5-trisphosphate 3-kinase distribution in the rat brain. High levels in the hippocampal CA1 pyramidal and cerebellar Purkinje cells suggest its involvement in some memory processes.

The distribution of inositol 1,4,5-trisphosphate (InsP3) 3-kinase was studied in the adult rat brain, using polyclonal antibodies raised against the purified 50,000-Da rat brain enzyme by immunohistochemistry and Western blot, in addition to enzymatic assay. Immunohistochemically, the enzyme was detected in neurons, where it was localized in the dendrites and at the periphery of the cell bodies. Using selective toxin lesions, the highest enzyme levels were found in the dendrites of hippocampal CA1 pyramidal cells and in neurons in the dorsal portion of the lateral septum, regions both involved in long-term potentiation; and in the dendrites of Purkinje cell subpopulations in the cerebellum, a region involved in long-term depression. High levels were found in neurons in the cortex; in the anterior olfactory nucleus; in the striatum (caudate, putamen, olfactory tubercle, Calleja islets and accumbens); in the central nucleus of the amygdala; in the hippocampal dentate gyrus and in the subiculum. The enzyme was not detected in other brain regions. By Western blot, a 50,000-Da immunoreactive band was present in the cortex, caudate-putamen and cerebellum. This band was most highly stained in the hippocampus. InsP3 3-kinase activity, stimulated by calcium/calmodulin, corresponded to 6172-2638 pmol of InsP4 produced/min/mg protein in the hippocampus followed by frontal and parietotemporal cortex and cerebellum. This activity was below 400 in the brainstem and spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Participation of postsynaptic PKC in cerebellar long-term depression in culture.

Long-term depression (LTD) in the intact cerebellum is a decrease in the efficacy of the parallel fiber-Purkinje neuron synapse induced by coactivation of climbing fiber and parallel fiber inputs. In cultured Purkinje neurons, a similar depression can be induced by iontophoretic glutamate pulses and Purkinje neuron depolarization. This form of LTD is expressed as a depression of alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid (AMPA)-mediated current, and its induction is dependent on activation of metabotropic quisqualate receptors. The effect of inhibitors of protein kinase C (PKC) on LTD induction was studied. Inhibitors of PKC blocked LTD induction, while phorbol-12,13-diacetate (PDA), a PKC activator, mimicked LTD. These results suggest that PKC activation is necessary for the induction of cerebellar LTD.

Animals↗

PubMed1991

Development of natural products as drugs acting on central nervous system.

We have recently studied several natural product constituents which have effects on the CNS. (1) Tetrahydropalmatine (THP) and its analogues were isolated from Corydalis ambigua and various species of Stephania. (+)-THP and (-)-THP possess not only analgesic activity, but also exert sedative-tranquilizing and hypnotic actions. Results of receptor binding assay and their pre- and post-synaptic effects on dopaminergic system indicate that (-)-THP and (-)-stepholidine are dopamine receptor antagonists while (+)-THP is a selective dopamine depletor. (2) 3-Acetylaconitine (AAC) is an alkaloid isolated from Aconitum flavum. The relative potency of analgesic action of AAC was 5.1-35.6 and 1250-3912 times that of morphine and aspirin, respectively. The analgesic effect of AAC was not antagonized by naloxone, but was eliminated by reserpine. In monkeys, after AAC was injected for 92 days, no abstinence syndrome was seen after sudden AAC withdrawal or when challenged with nalorphine. (3) Huperzine A (Hup-A) is an alkaloid isolated from Huperzia serrata which was found to be a selective ChE inhibitor and could improve learning and retrieval processes. Preliminary clinical studies showed that Hup-A improve short- and long-term memory in patients of cerebral arteriosclerosis with memory impairment. (4) Ranamargarin is a new tetradecapeptide isolated from the skin of the Chinese frog Rana margaratae. This peptide may mainly act on NK-1 receptor.

Amino Acid Sequence↗

PubMed1990

Differential effect of gepirone on presynaptic and postsynaptic serotonin receptors: single-cell recording studies.

The sustained administration of the serotonin (5-hydroxytryptamine1A, 5-HT1A) agonist gepirone (15 mg/kg/day subcutaneously) in the rat produced an initial decrease of the firing activity of dorsal raphe 5-HT neurons, which was followed by a progressive recovery to normal after 14 days of treatment. At this point, the somatodendritic 5-HT1A autoreceptor had desensitized, as indicated by the reduced effectiveness of intravenous lysergic acid diethylamide (LSD) and of microiontophoretic applications of 5-HT, LSD, 8-hydroxy-2-(N,N-propylamino) tetralin (8-OH-DPAT), and gepirone, but not of gamma-aminobutyric acid in depressing the firing activity of 5-HT neurons. In contrast, the responsiveness of postsynaptic dorsal hippocampus pyramidal neurons to 5-HT, 8-OH-DPAT, and gepirone was not altered by the 14-day gepirone treatment. In an attempt to unravel the differential effect of sustained gepirone administration on presynaptic and postsynaptic 5-HT1A receptors, the properties of gepirone at these two receptors were assessed. The concurrent microiontophoretic application of gepirone readily blocked the effect of 5-HT on dorsal hippocampus pyramidal neurons, but not on dorsal raphe 5-HT neurons, thus indicating that gepirone is a partial agonist at postsynaptic 5-HT1A receptors and a full agonist at somatodendritic 5-HT1A receptors. It is proposed that gepirone, being a partial agonist at postsynaptic 5-HT1A receptors, fails to desensitize them; whereas, because of its full agonistic activity at the somatodendritic 5-HT1A receptor, it desensitizes this autoreceptor with long-term administration.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

Use-dependent fade and slow recovery of long-term potentiation in superior cervical ganglion of the cat.

1. In anesthetized cats under partial block of nicotinic ganglionic transmission by hexamethonium and in which the cervical sympathetic trunk (CST) was split into two bundles of approximately equal size, a 40-Hz 5-s conditioning stimulus train to one bundle produced prolonged potentiation of the postganglionic compound action potential evoked by a test stimulus to the same or to the other bundle [homosynaptic and heterosynaptic, respectively, long-term potentiation (LTP)]. The LTP was detected also by recording the nictitating membrane (NM) contraction in response to a test preganglionic train. 2. The homosynaptic or heterosynaptic LTP produced by applying the conditioning 40-Hz 5-s train to one bundle was markedly depressed in amplitude and duration after stimulation of that bundle at 40 Hz for 20 min, whereas the homosynaptic or heterosynaptic LTP produced by applying the conditioning 40-Hz 5-s train to the other bundle was unchanged. The latter evidence suggests that all superior cervical ganglion (SCG) synapses can still express LTP during the depression that follows the 40-Hz 20-min train. 3. In 4 h there was no appreciable recovery of LTP from the depression produced by a 40-Hz 20-min train (n = 5). However, after 3 days (n = 3) and 5 days (n = 3), LTP recovered to 53 and 90% of control, respectively. 4. When colchicine was applied to the CST bilaterally, at a concentration sufficient to block fast axonal transport, and one CST only was stimulated for 20 min at 40 Hz, the LTP recorded 4 days later was significantly smaller on the stimulated than on the contralateral, control, side.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1991

Long-term potentiation of nicotinic transmission by a heterosynaptic mechanism in the stellate ganglion of the cat.

1. In the anesthetized, scopolamine-treated cat, the compound action potential (CAP) evoked by a single supramaximal shock to the third thoracic white ramus (T3WR) was recorded in the inferior cardiac nerve (ICN). The CAP was depressed in a dose-dependent manner by the intravenous administration of the nicotinic antagonist hexamethonium (C6). 2. During steady intravenous infusion of C6, which reduced the amplitude of the CAP by 80-90%, a short train of stimuli (few seconds, 10-40 Hz) to the sympathetic trunk just below T4WR potentiated the CAP for periods of tens of minutes to 1-2 h (heterosynaptic long-term potentiation, LTP). An LTP of similar time course was obtained when both train and single shock were applied to T3WR (homosynaptic LTP). Magnitude and duration of the heterosynaptic LTP were dependent on number, frequency, and intensity of the stimuli. No LTP was produced by a train to the ICN. Heterosynaptic LTP was also observed in the absence of C6. Because of the limited subliminal fringe of the test input under this condition, the LTP was of small magnitude. Heterosynaptic LTP also of the heart rate (HR) response to a test stimulus was observed after a conditioning train. 3. The conditioning train produced a displacement to the right of the dose-response curve for C6. The intravenous dose of C6 required for 50% attenuation of the test CAP increased from 0.84 +/- 0.15 (SE) mg/kg pretrain to 2.56 +/- 0.46 mg/kg posttrain (n = 5, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1990

Striatal preprotachykinin and preproenkephalin mRNA levels and the levels of nigral substance P and pallidal Met5-enkephalin depend on corticostriatal axons that use the excitatory amino acid neurotransmitters aspartate and glutamate: quantitative radioimmunocytochemical and in situ hybridization evidence.

Because excitatory amino acid (EAA) neurotransmission has been implicated in long-term postsynaptic events, we conducted an initial study to determine whether or not the EAA-utilizing corticostriatal projection might influence peptide biosynthesis in neurons of the rat's basal ganglia. The content of EAAs in the caudatoputamen was reduced by frontal cortical ablation or by chronic intracerebroventricular infusion of methionine sulfoximine (MS). At 7 days following cortical ablation striatal Asp and Glu were reduced by 15% and 24%, respectively, while MS infusion (24 micrograms/day) for 7 days reduced synaptosomal levels of Asp by 61% and Glu by 48%. With either treatment, quantitative radioimmunocytochemistry revealed that substance P (SP) in the substantia nigra was increased by approximately 38%, while Met5-enkephalin (ME) in the globus pallidus was not changed. In situ hybridization with oligonucleotide probes revealed changes in the rostral striatum of preprotachykinin (PPT) and preproenkephalin (PPE) mRNA levels: cortical ablation reduced PPT mRNA by 17% and PPE mRNA by 20% dorsally, while it increased PPE mRNA (but not PPT mRNA) by 23% ventrally. Likewise, the infusion of MS decreased PPT (32%) and PPE mRNA (28%) dorsally, and increased PPE mRNA (50%) ventrally. In addition to the 7 day time point, the same measurements of EAAs, peptides and mRNAs were made at 14, 21 and 28 days after cortical excisions. At 14 days, the level of striatal Asp had returned to control value, but Glu remained depressed by 21%; nigral SP remained increased by 24%, and pallidal ME decreased by 15%. PPT and PPE mRNA remained depressed dorsally by 15% and 25%, respectively, while the increase in PPE mRNA noted ventrally at 7 days had returned to control values by 14 days. With the exception of Glu, which remained depressed by 18% at 21 and 28 days, all other values had returned to control levels by 21 days. The results indicate that a large reduction in EAA neurotransmission can influence differentially the steady-state levels of neuropeptides in striatal neurons and this change is brought about, at least in part, by an alteration in gene transcription.

Animals↗

PubMed1990

Long-term potentiation in rat hippocampus is inhibited by low concentrations of ethanol.

Acute ethanol ingestion impairs memory in humans at concentrations associated with mild intoxication. A possible neurophysiological correlate of this effect is the suppression by ethanol of long-tem potentiation (LTP), a persistent increase in synaptic efficiency which has been proposed as a substrate for memory. However, in previous studies ethanol has been shown to impair LTP only at very high concentrations, near the lethal level in humans. We now report that ethanol can significantly reduce LTP in rat hippocampus at concentrations as low as 5 mM, a level attainable following ingestion of a single alcoholic drink. We also demonstrate that the potency of ethanol in depressing LTP correlates well with its potency in inhibiting the response to N-methyl-D-aspartate, an agonist at the glutamate receptors implicated in LTP induction. The influence of low ethanol concentrations on LTP may contribute to the memory impairment associated with its use in humans.

Animals↗

PubMed1992

Long-term potentiation induced by patterned stimulation of the commissural pathway to hippocampal CA1 region in freely moving rats.

In urethane-anesthetized rats, stimulation of the contralateral hippocampal CA1 region resulted in activation of the homotopic CA1 region. Current-source-density analysis revealed that both basal and apical dendrites were activated. However, alveolar and stratum oriens stimulation in CA1 gave about equal peak excitation of the basal and apical dendrites while CA1 stratum radiatum/moleculare and CA3c stimulation gave stronger apical than basal dendritic excitation. In chronically implanted and freely moving rats, tetanic patterned stimulation of the contralateral CA1, irrespective of depth, resulted in a robust long-term potentiation of the ipsilateral CA1 basal dendritic synapse. The population basal dendritic excitatory postsynaptic potential was initially potentiated to greater than 200% of the baseline and decayed with a 3 h time constant; it lasted at least two days. Patterned stimulation of the commissural inputs at 2 x threshold stimulus intensity seldom potentiated the apical dendritic synapse in CA1; rather, long-term depression was sometimes observed. After tetanic stimulations at 3 x threshold, a small potentiation of the apical dendritic excitation was seen in about half of the experiments. The average apical dendritic potentiation peaked at about 25% and persisted to at least one day. This study provides original evidence that the properties of long-term potentiation are different at the commissural basal dendritic and apical dendritic synapses in CA1 of the behaving rat. Basal dendritic potentiation is low-threshold, high-amplitude and decayed rapidly in the first 3 h. Apical dendritic potentiation is high-threshold, low-amplitude and not rapidly decaying. A long-lasting enhancement of synaptic transmission has been postulated as a physiological correlate of memory. This paper reports properties of this synaptic enhancement for two different types of synapses on the same cells in the behaving animal. The basal dendritic synapse on hippocampal pyramidal cells readily increased their efficacy, up to at least two days, after a brief, patterned stimulation. In the same preparation, it was difficult to obtain a long-lasting increase in the apical dendritic excitation, in contrast to studies on isolated hippocampal slices in vitro.

Animals↗