Biomedical subjects

John M Horowitz

Publications and source records attributed to John M Horowitz.

5 recordsLinked to original sources

PubMed2006

Temperature modifies potentiation but not depotentiation in bidirectional hippocampal plasticity of Syrian hamsters (Mesocricetus auratus).

Previous studies have shown that one form of neuroplasticity, population spike (PS) potentiation, can be established in the hamster hippocampus at temperatures above 20 degrees C. Here, we tested three related hypotheses; namely, that in Syrian hamsters: (1) PS potentiation can be elicited below 20 degrees C and that at any constant temperature, potentiation can be described by a pair of sigmoidal functions matched to input/output curves; (2) potentiation can be partially reversed by depotentiation (a second and distinctive form of neuroplasticity); and (3) tetanus evokes long-term potentiation in slices from animals housed under conditions corresponding to various stages of the annual hibernation cycle. To test these hypotheses, we measured PS amplitudes and fEPSP slopes in CA1 pyramidal cells in hippocampal slices. We found that sigmoidal functions before and after tetanus showed PS enhancement at 18 degrees C and a larger enhancement at 28 degrees C, thereby supporting hypothesis 1. We also found that low-frequency stimulation reduced the amplitude of the potentiated PS by approximately 29% at both 18 degrees C and 28 degrees C, consistent with hypothesis 2; and that slices from nonhibernating hamsters on long and short photoperiods and from hamsters in hibernation all showed at least 40% increases in fEPSP slope following tetanus at a slice temperature of 23 degrees C, supporting hypothesis 3. Thus, bidirectional plasticity is present in hamsters. That is, both potentiation and depotentiation were readily evoked at 28 degrees C; potentiation was muted, while depotentiation (the reversal of the potentiation) remained robust at 18 degrees C. Moreover, potentiated responses could be elicited in slices from animals housed under diverse conditions.

Animals↗

PubMed2005

LOXL null mice demonstrate selective dentate structural changes but maintain dentate granule cell and CA1 pyramidal cell potentiation in the hippocampus.

Lysyl oxidase-like protein (LOXL), part of the lysyl oxidase copper-dependent amine oxidase family, is expressed in the extracellular matrix and in the nucleus. It likely plays a role in cross-linking collagen and elastin, possibly modulating cellular functions. Immunohistochemical studies show the presence of LOXL in the pyramidal cell layer of the hippocampus; and in this study, we report that cells in the granule cell layer have significantly smaller somas in LOXL -/- compared to LOXL +/+ mice. In addition we tested the hypothesis that these structural alterations in the dentate granule layer were associated with synaptic efficacy and thus muted long-term potentiation in mice lacking the protein. Electrical recordings were obtained in 300-mum hippocampal slices in dentate and CA1 pyramidal cell layers in age-matched wild type and LOXL null mice. Potentiation in the CA1 cell layer of 10 LOXL -/- and 8 LOXL +/+ mice was 191.0+/-9.3% and 181.6+/-9.1%, respectively (mean+/-S.E.M.). Dentate potentiation was 120.8+/-7.0% and 121.0+/-3.4% in 11 LOXL -/- and 11 LOXL +/+ mice, respectively. No phenotypic difference in potentiation of population spike amplitude (or in EPSP slope) in either layer was observed. Thus, contrary to expectation, structural changes in the hippocampus of LOXL -/- mice did not affect synaptic remodeling in a manner that impaired the establishment of LTP.

Amino Acid Oxidoreductases↗

PubMed2004

Neural plasticity is impaired in cold-exposed hippocampal slices from senescent but not from age-matched presenescent F344 rats.

Near the end of their natural life, many mammals enter a terminal state identifiable by a rapid loss of body weight resulting from hypophagia. This study extends characterization of this senescent state by comparing viability of metabolic mechanisms supporting neural plasticity in hippocampal slices from 24 to 30 month old senescent and age-matched presenescent (body-weight stable) F344 male rats. Half of the slices from each rat were incubated at 22-23 degrees C, and half were immersed in cool incubation medium (12-15 degrees C) immediately after slicing and allowed to passively warm to room temperature over approximately 50 min to impose a cold stressor on recovery mechanisms. Following incubation, CA1 pyramidal cell population spike (PS) amplitudes were measured before and after tetanus. In slices incubated at 22-23 degrees C, the 221.0+/-24.2 % increase in PS amplitude following tetanus in seven slices from five senescent rats was not significantly different from the 202.5+/-23.8% increase in six slices from five age-matched presenescent rats. In contrast, in cold-exposed slices, the 133.8+/-13.1% increase in PS amplitude following tetanus in 14 slices from 10 senescent rats was significantly smaller (p<0.05) than the 184.7+/-10.2% increase in 13 slices from seven age-matched presenescent rats. This smaller PS enhancement in senescent rats cannot be attributed to weight loss because robust potentiation was induced in cold-exposed slices from five food-restricted presenescent rats having a weight loss comparable to their senescent counterparts. Thus, the blunted enhancement observed in cold-exposed slices appears to be a characteristic of senescence.

Aging↗

PubMed2002

Enhanced adrenergic excitation of serotonergic dorsal raphe neurons in genetically obese rats.

Serotonergic neurons in the dorsal raphe nucleus (DRN) project to the ventromedial hypothalamus (VMH), where serotonin (5-HT) release modulates feeding. 5-HT release in the VMH is altered in genetically obese vs. lean Zucker rats. Serotonergic DRN neurons are subject to adrenergic and serotonergic neuromodulation. To determine if the difference in 5-HT release between lean and obese rats might be due to differences in these neuromodulatory pathways, we examined the effects of phenylephrine (PE) and 5-HT on serotonergic DRN neurons using current-clamp recording. Cells from lean and obese animals responded similarly to 5-HT, but cells from obese rats exhibited both a larger depolarization and increased firing rate in response to PE than did cells from lean rats. This indicates that DRN neurons of obese rats have an enhanced adrenergic drive.

Adrenergic alpha-Agonists↗

PubMed2002

Synaptic transmission in nucleus tractus solitarius is depressed by Group II and III but not Group I presynaptic metabotropic glutamate receptors in rats.

Presynaptic metabotropic glutamate receptors (mGluRs) serve as autoreceptors throughout the CNS to inhibit glutamate release and depress glutamatergic transmission. Both presynaptic and postsynaptic mGluRs have been implicated in shaping autonomic signal transmission in the nucleus tractus solitarius (NTS). We sought to test the hypothesis that activation of presynaptic mGluRs depresses neurotransmission between primary autonomic afferent fibres and second-order NTS neurones. In second-order NTS neurones, excitatory postsynaptic currents (EPSCs) synaptically evoked by stimulation of primary sensory afferent fibres in the tractus solitarius (ts) and currents postsynaptically evoked by alpha-amino-3-hydroxy-4-isoxazoleproprionic acid (AMPA) were studied in the presence and absence of mGluR agonists and antagonists. Real-time quantitative RT-PCR (reverse transcription-polymerase chain reaction) was used to determine whether the genes for the mGluR subtypes were expressed in the cell bodies of the primary autonomic afferent fibres. Agonist activation of Group II and III but not Group I mGluRs reduced the peak amplitude of synaptically (ts) evoked EPSCs in a concentration-dependent manner while having no effect on postsynaptically (AMPA) evoked currents recorded in the same neurones. At the highest concentrations, the Group II agonist, (2S,3S,4S)-CCG/(2S,1'S,2'S)-2-carboxycyclopropyl (L-CCG-I), decreased the amplitude of the ts-evoked EPSCs by 39 % with an EC50 of 21 microM, and the Group III agonist, L(+)-2-amino-4-phosphonobutyric acid (L-AP4), decreased the evoked EPSCs by 71 % with an EC50 of 1 mM. mRNA for all eight mGluR subtypes was detected in the autonomic afferent fibre cell bodies in the nodose and jugular ganglia. Group II and III antagonists ((2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)glycine (MCCG) and (RS)-alpha-methylserine-O-phosphate (MSOP)), at concentrations that blocked the respective agonist-induced synaptic depression, attenuated the frequency-dependent synaptic depression associated with increasing frequencies of ts stimulation by 13-34 % and 13-19 %, respectively (P < 0.05, for each). We conclude that Group II and III mGluRs (synthesized in the cell bodies of the primary autonomic afferent fibres and transported to the central terminals in the NTS) contribute to the depression of autonomic signal transmission by attenuating presynaptic release of glutamate.

Amino Acids, Dicarboxylic↗