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M J Rowan

Publications and source records attributed to M J Rowan.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prognostic value of electrophysiological markers in Alzheimer's disease.

The authors assessed the usefulness of event-related potentials (ERP) and flash visual evoked potentials (FVEP) as prognostic markers in a sample of 25 subjects with probable Alzheimer's disease (AD). ERP and FVEP recordings were obtained from 21 and 23 subjects, respectively. Ranking of the annual rate of change in cognitive scales vs. baseline ERP/FVEP latencies was compared, and those with longer FVEP N(2) component latencies showed slower subsequent rates of decline (tau=0.32; z=2.16; P=0.015), suggesting that further study of FVEP responses as prognostic markers in AD is warranted.

Aged↗
PubMed1998

Role of protein kinase C in the induction of homosynaptic long-term depression by brief low frequency stimulation in the dentate gyrus of the rat hippocampus in vitro.

1. Enhancement of the induction of long-term depression (LTD) of excitatory postsynaptic currents (EPSCs) by a priming stimulus was investigated in the medial perforant pathway of the dentate gyrus of the hippocampus in vitro. 2. In control, LTD could be induced by a conditioning low frequency stimulation (LFS) consisting of sixty, although not thirty or fewer, stimuli at 1 Hz applied at a holding potential of -40 mV. 3. A conditioning LFS of just five stimuli at 1 Hz was found to induce LTD if preceded 1-5 min, but not 15 min, by a priming LFS of five stimuli at 1 Hz, -40 mV, which did not by itself induce LTD. 4. A low concentration of the protein kinase C (PKC) activator (-)-indolactam V, which did not itself induce LTD, reduced the threshold for the number of stimuli inducing LTD following the priming stimulus, while a high concentration of (-)-indolactam V directly induced a depression of the test excitatory postsynaptic current (EPSC), which occluded LFS-induced LTD. This suggests that the priming of LTD and also the direct induction of LTD involves the activation of PKC. 5. The pseudosubstrate peptide inhibitor PKC19-36 inhibited the induction of LTD by the priming protocol and by the control induction conditioning protocol. 6. These experiments demonstrate that a covert synaptic change involving generation of PKC is very effective in producing conditions whereby LTD is induced by very brief synaptic stimulation.

Animals↗
PubMed1998

Induction of LTD by increasing extracellular Ca2+ from a low level in the dentate gyrus in vitro.

Long-term depression (LTD) of field excitatory postsynaptic potentials was induced in the medial path of the dentate gyrus in juvenile rats in vitro by a protocol involving returning the Ca2+ concentration of the external media to the control level (2 mM) following a period (30 min) in low Ca2+ (1.2 mM), with stimulation at the test frequency throughout. Directly increasing Ca2+ from the control level did not induce LTD (or long-term potentiation). Such LTD showed mutual occlusion with low frequency stimulation (LFS, 1 Hz, 900 stimuli)-induced LTD. The Ca2+-induced LTD was shown to be induced by the procedure of elevating the Ca2+ from the low to the control concentration, and not by the procedure of lowering of Ca2+, as full amplitude LFS induced LTD could be induced in the low Ca2+ media. Ca2+-induced LTD was inhibited by Ni2+ (25 microM) and 2-amino-5-phosphonopentanoate (50 microM), demonstrating the necessity for activation of T/R-type voltage-gated Ca2+ channels and N-methyl-D-aspartate receptors, respectively.

2-Amino-5-phosphonovalerate↗
PubMed1998

Presynaptic inhibitory action of the group II metabotropic glutamate receptor agonists, LY354740 and DCG-IV.

Electrophysiological studies were carried out on the presynaptic inhibitory action of the group II metabotropic glutamate (mGlu) receptor agonists (+)-2-aminobicyclo[3.1.0]hexane-2-6-dicarboxylic acid (LY354740) and (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) in three paths of the rat hippocampus, the medial and lateral perforant path to the dentate gyrus, and the Schaffer collateral/commissural path to CA1. LY354740 caused a dose-dependent reversible inhibition of the field excitatory postsynaptic potential (EPSP) in the medial and lateral perforant paths, with an EC50 of 115 +/- 16 nM and 230 +/- 58 nM, respectively. Maximal inhibition by LY354740 was much greater in the medial path (about 80%) than in the lateral path (about 50%). No inhibition was observed in CA1. A presynaptic inhibition was confirmed by LY354740 inducing dose-dependent changes in paired-pulse depression/facilitation. DCG-IV had a similar action to LY354740, but with a lower potency.

Animals↗
PubMed1998

Spatial exploration induces a persistent reversal of long-term potentiation in rat hippocampus.

Experience-dependent long-lasting increases in excitatory synaptic transmission in the hippocampus are believed to underlie certain types of memory. Whereas stimulation of hippocampal pathways in freely moving rats can readily elicit a long-term potentiation (LTP) of transmission that may last for weeks, previous studies have failed to detect persistent increases in synaptic efficacy after hippocampus-mediated learning. As changes in synaptic efficacy are contingent on the history of plasticity at the synapses, we have examined the effect of experience-dependent hippocampal activation on transmission after the induction of LTP. We show that exploration of a new, non-stressful environment rapidly induces a complete and persistent reversal of the expression of high-frequency stimulation-induced early-phase LTP in the CA1 area of the hippocampus, without affecting baseline transmission in a control pathway. LTP expression is not affected by exploration of familiar environments. We found that spatial exploration affected LTP within a defined time window because neither the induction of LTP nor the maintenance of long-established LTP was blocked. The discovery of a novelty-induced reversal of LTP expression provides strong evidence that extensive long-lasting decreases in synaptic efficacy may act in tandem with enhancements at selected synapses to allow the detection and storage of new information by the hippocampus.

Animals↗
PubMed1998

Evidence for involvement of the cGMP-protein kinase G signaling system in the induction of long-term depression, but not long-term potentiation, in the dentate gyrus in vitro.

The involvement of the cGMP-protein kinase G (PKG) signaling pathway in the induction of long-term depression (LTD) and long-term potentiation (LTP) was investigated in the medial perforant path of the dentate gyrus in vitro. Low-frequency stimulation (LFS)-induced LTD of field EPSPs was inhibited by bath perfusion of the selective soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3, -a]quinoxalin-1-one (ODQ). LFS-induced LTD of EPSPs and whole-cell patch-clamped EPSCs was also blocked by bath perfusion and postsynaptic intracellular injection, respectively, of the selective PKG inhibitor KT5823. Elevation of intracellular cGMP by perfusion of the cGMP phosphodiesterase inhibitor zaprinast resulted in induction of LTD of field EPSPs and EPSCs. Occlusion experiments showed mutual inhibition between LFS-induced LTD and zaprinast-induced LTD. The zaprinast-induced LTD of field EPSPs was inhibited by perfusion of ODQ and KT5823. In addition, zaprinast-induced LTD of EPSCs was inhibited by postsynaptic application of KT5823. Glutamate receptor stimulation, especially that of metabotropic glutamate receptors (mGluRs), was required for zaprinast-induced LTD, because cessation of test stimulation or perfusion with the mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) inhibited zaprinast-induced LTD. No inhibitory effect of ODQ or KT5823 on the induction of LTP of EPSPs or EPSCs was found. These data indicate that the cGMP-guanyly cyclase-PKG signaling pathway in the dentate gyrus is essential for induction of LTD, although not of LTP, in the dentate gyrus.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

Glucocorticoid receptor and protein/RNA synthesis-dependent mechanisms underlie the control of synaptic plasticity by stress.

Learning and memory are exquisitely sensitive to behavioral stress, but the underlying mechanisms are still poorly understood. Because activity-dependent persistent changes in synaptic strength are believed to mediate memory processes in brain areas such as the hippocampus we have examined the means by which stress affects synaptic plasticity in the CA1 region of the hippocampus of anesthetized rats. Inescapable behavioral stress (placement on an elevated platform for 30 min) switched the direction of plasticity, favoring low frequency stimulation-induced decreases in synaptic transmission (long-term depression, LTD), and opposing the induction of long-term potentiation by high frequency stimulation. We have discovered that glucocorticoid receptor activation mediates these effects of stress on LTD and long-term potentiation in a protein synthesis-dependent manner because they were prevented by the glucocorticoid receptor antagonist RU 38486 and the protein synthesis inhibitor emetine. Consistent with this, the ability of exogenously applied corticosterone in non-stressed rats to mimic the effects of stress on synaptic plasticity was also blocked by these agents. The enablement of low frequency stimulation-induced LTD by both stress and exogenous corticosterone was also blocked by the transcription inhibitor actinomycin D. Thus, naturally occurring synaptic plasticity is liable to be reversed in stressful situations via glucocorticoid receptor activation and mechanisms dependent on the synthesis of new protein and RNA. This indicates that the modulation of hippocampus-mediated learning by acute inescapable stress requires glucocorticoid receptor-dependent initiation of transcription and translation.

Animals↗
PubMed1998

(+)-MCPG blocks induction of LTP in CA1 of rat hippocampus via agonist action at an mGluR group II receptor.

We investigated the effect of metabotropic glutamate receptor (mGluR) ligands on the induction of long-term potentiation (LTP) of field excitatory postsynaptic potentials (EPSPs) in CA1 of rat hippocampus, in particular the manner by which the nonsubtype selective mGluR ligand alpha-methyl-4-carboxyphenylglycine [(+)-MCPG] blocks LTP induction. Normalized control LTP was blocked by (+)-MCPG (250 microM), but not by the mGluRI selective antagonist (S)-4-carboxyphenylglycine (4-CPG), the mGluRII selective antagonist 1/(2S,3S, 4S)-2-methyl-2-(carboxycyclopropyl) glycine (MCCG), or the mGluRIII antagonist (S)-2-amino-2-methyl-4-phosphonobutanoic acid/alpha-methyl (MAP4). In contrast the mGluRII agonist ((1S, 3S)-1-aminocyclopentante-1,3-dicarboxylic acid -(1S,3S)-ACPD-; 10 or 25 microM) completely and consistently blocked LTP. The block of LTP by both (1S,3S)-ACPD and (+)-MCPG could be prevented by preincubation with the mGluRII antagonist MCCG. These studies demonstrate that (+)-MCPG blocks LTP induction through an agonist action at an mGluRII receptor and not through a nonselective antagonist action.

Amino Acids, Dicarboxylic↗
PubMed1997

Block of LTP in rat hippocampus in vivo by beta-amyloid precursor protein fragments.

The effects of beta-amyloid precursor protein (beta-APP) fragments on plasticity of glutamtatergic synaptic transmission were examined in the hippocampus of urethane anaesthetized rats. I.c.v. injection of beta-amyloid (A beta) 1-40 and 1-42 and the C-terminal fragment CT105 greatly shortened the duration of high frequency stimulation-induced long-term potentiation (LTP) of field excitatory postsynaptic potentials in the CA1 area. Whereas in vehicle injected animals LTP was stable over a 5 h recording period, doses of these peptides (A beta 1-40, 0.4 and 3.5 nmol; A beta1-42, 0.01 nmol; CT105, 0.05 nmol) which did not affect baseline synaptic transmission abolished LTP within 3-5 h. The reduced duration of this form of synaptic plasticity may contribute to the cognitive deficits in Alzheimer's disease.

Amyloid beta-Protein Precursor↗
PubMed1997

Stimulation on the positive phase of hippocampal theta rhythm induces long-term potentiation that can Be depotentiated by stimulation on the negative phase in area CA1 in vivo.

Long-term potentiation (LTP) of synaptic transmission induced by high-frequency stimulation (HFS) is considered to be a model for learning processes; however, standard HFS protocols consisting of long trains of HFS are very different from the patterns of spike firing in freely behaving animals. We have investigated the ability of brief bursts of HFS triggered at different phases of background theta rhythm to mimic more natural activity patterns. We show that a single burst of five pulses at 200 Hz given on the positive phase of tail pinch-triggered theta rhythm reliably induced LTP in the stratum radiatum of the hippocampus of urethane-anesthetized rats. Three of these bursts saturated LTP, and 10 bursts occluded the induction of LTP by long trains of HFS. Burst stimulation on the negative phase or at zero phase of theta did not induce LTP or long-term depression. In addition, stimulation with 10 bursts on the negative phase of theta reversed previously established LTP. The results show that the phase of sensory-evoked theta rhythm powerfully regulates the ability of brief HFS bursts to elicit either LTP or depotentiation of synaptic transmission. Furthermore, because complex spike activity of approximately five pulses on the positive phase of theta rhythm can be observed in freely moving rats, LTP induced by the present theta-triggered stimulation protocol might model putative synaptic plastic changes during learning more closely than standard HFS-induced LTP.

Anesthetics, Intravenous↗
PubMed1997

PCCG-IV inhibits the induction of long-term potentiation in the dentate gyrus in vitro.

The effects of two ligands with previously established high and selective potency for metabotropic glutamate receptors (mGlu receptors) group II have been investigated on the high frequency stimulation (HFS) induced long-term potentiation of the field excitatory postsynaptic potential (EPSP) in the dentate gyrus of the rat hippocampus in vitro. The ligands investigated were (2S,1'S,2'S,3'R)-2-(2"-carboxy-3'-phenylcyclopropyl)glycine (PCCG-IV) and (R,S)-alpha-methyl-4-tetrazolylphenylglycine (MTPG). PCCG-IV (10 microM) strongly inhibited the induction of long-term potentiation of the field EPSP by high frequency stimulation. MTPG (50 microM) did not inhibit the induction of long-term potentiation, but prevented the inhibition of long-term potentiation induction by PCCG-IV. The inhibition of long-term potentiation induction by PCCG-IV is suggested to be due to an agonistic action on mGlu receptor group II, probably mGlu3 receptor, as the inhibition of long-term potentiation can be reversed by the application of MTPG, a well-known selective and potent antagonist of mGlu receptor group II.

Alanine↗
PubMed1997

Behavioural stress facilitates the induction of long-term depression in the hippocampus.

The induction of activity-dependent persistent increases in synaptic efficacy, such as long-term potentiation (LTP), is inhibited by behavioural stress. The question arises whether stress also affects the ability to induce persistent decreases in synaptic efficacy, such as long-term depression (LTD). We now report that the induction of stable homosynaptic LTD in the CA1 area of the hippocampus of awake adult rats is facilitated, rather than inhibited, by exposure to mild naturalistic stress. The same stress blocked the induction of LTP. The effects of such stress were short lasting: acclimatization to, or removal from, the conditions that facilitated LTD induction led to a rapid loss of the ability to elicit this form of plasticity. The time window in which LTD could be reliably elicited was prolonged by inducing anaesthesia immediately after the stress. These data reveal that even brief exposure to mild stress can produce a striking shift in the susceptibility to synaptic plasticity in the awake animal.

Animals↗
PubMed1997

Effect of repeated ipsapirone treatment on hippocampal excitatory synaptic transmission in the freely behaving rat: role of 5-HT1A receptors and relationship to anxiolytic effect.

The effects of acute and repeated treatment with the 5-HT1A receptor ligand ipsapirone on hippocampal excitatory synaptic transmission and in an ultrasonic vocalization anxiety test were investigated in the rat. Synaptic responses in the CA1 region of the dorsal hippocampus of alert, freely behaving male Wistar rats were reduced after acute injection of ipsapirone (1 or 2 mg/kg, i.p.). This effect was prevented by pretreatment with the 5-HT1A receptor antagonist WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide trihydrochloride, 0.25 or 0.5 mg/kg, i.p.) but not by the 5-HT-depleting agent para-chlorophenylalanine (300 mg/kg per day for 3 days, i.p.). WAY-100635 (0.1-0.3 mg/kg, i.p.) also blocked the acute anti-aversive effects of ipsapirone (3 mg/kg, i.p.) in the anxiety test. Repeated administration of ipsapirone (1 or 2 mg/kg per day for 7-8 days, i.p.) produced a gradual reduction in baseline synaptic transmission which was transiently reversed by WAY-100635 (0.25 mg/kg, i.p.). Ipsapirone (1 mg/kg per day for 7 days) produced a gradual and sustained reduction in the duration of vocalizations in the anxiety test which paralleled the reduction in baseline synaptic responses in the same animals. The data indicate that with repeated administration of ipsapirone, a prolongation and enhancement of the 5-HT1A receptor-mediated reduction in hippocampal excitatory synaptic transmission occurs. This delayed effect may contribute to the sustained anxiolytic and/or antidepressant effect of ipsapirone.

Animals↗
PubMed1997

Activation of group-II metabotropic glutamate receptors blocks induction of long-term potentiation and depotentiation in area CA1 of the rat in vivo.

The metabotropic glutamate receptor group-II agonist (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3S-ACPD; 5 microliters/10 mM, i.c.v.) prevented the induction of long-term potentiation and depotentiation in the CA1 area of the hippocampus in urethane-anaesthetised rats. These effects were prevented by the group-II metabotropic glutamate receptor antagonists alpha-methyl-(2S,3S,4S)-alpha-(carboxycyclopropyl)glycine (MCCG; 5 microliters/100 mM) and (RS)-alpha-methyl-4-tetrazolylphenylglycine (MTPG; 5 microliters/500 mM). The group-I antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 5 microliters/200 mM) or the group-III antagonist alpha-methyl-L-2-amino-4-phosphonobutyrate (MAP4; 5 microliters/100 mM) did not affect the block of the induction of long-term potentiation by 1S,3S-ACPD. It is concluded that activation of group-II metabotropic glutamate receptors can block both high-frequency stimulation-induced long term potentiation and low-frequency stimulation-induced depotentiation in the CA1 area in vivo.

Animals↗
PubMed1997

DCG-IV inhibits synaptic transmission by activation of NMDA receptors in area CA1 of rat hippocampus.

We investigated the synaptic depressant action of the metabotropic glutamate receptor group II agonist, (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-glycine (DCG-IV), in area CA1 of rat hippocampus. A brief bath application of DCG-IV (10 microM) caused a rapidly reversible depression to 0.57 +/- 0.22 (i.e., 43%) of baseline excitatory postsynaptic potential (epsp) slope. This depression could not be attenuated by the metabotropic glutamate receptor antagonists alpha-methyl-L-CCGI/(2S,3S,4S)-2-methyl-2-(carboxycyclopropyl++ +)glycine (MCCG), (RS)-alpha-methyl-4-tetrazolyphenylglycine (MTPG) or (S)-2-amino-2-methyl-4-phosphonobutanoic acid alpha-methyl-AP4) (MAP4). However, the DCG-IV-induced depression could be reversed by the NMDA receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid (AP5; 50 microM), and partially reversed by the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 5 microM). These results strongly suggest that DCG-IV is an agonist at NMDA receptors and provide further evidence against a role for metabotropic glutamate receptor group II in synaptic transmission in area CA1 of rat hippocampus.

2-Amino-5-phosphonovalerate↗
PubMed1997

mGluR II agonist inhibition of LTP induction, and mGluR II antagonist inhibition of LTD induction, in the dentate gyrus in vitro.

The effects of the metabotropic glutamate receptor (mGluR) group II agonist (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) and the antagonist 2S,1S',2S'-2-methyl-2-(2'-carboxycyclopropyl)glycine (MCCG) on the induction of long-term potentiation (LTP) and long-term depression (LTD) of the field excitatory postsynaptic potential (epsp) in the dentate gyrus of the rat hippocampus were investigated in vitro. In control media, high frequency stimulation (HFS) consisting of a series of trains of stimuli at 200 Hz induced LTP, and low frequency stimulation (LFS) consisting of 900 stimuli at 1 Hz induced LTD. DCG-IV (50 nM) strongly inhibited the induction of LTP. The block of LTP induction was not caused by a frequency-dependent inhibition of the epsp during HFS, as the epsps evoked during HFS were not altered by DCG-IV. MCCG (500 microM) did not inhibit the induction of LTP, but did prevent the block of LTP by DCG-IV. MCCG (500 microM) strongly inhibited the induction of LTD. DCG-IV (50 nM) did not inhibit LTD induction.

Amino Acids, Dicarboxylic↗