GLUTAMINE AUGMENTS NEURONAL NETWORK ACTIVITY IN RAT HIPPOCAMPAL SLICES
AbstractBackground: In recent past, a huge number of in vitro electrophysiological techniques have been developed to explore underlying mechanisms of most complicated functions of brain. Neurophysiologist and neuroscientist use different compositions of artificial cerebrospinal fluid (aCSF) usually based on ionic and energy demands of neurons but these compositions lack amino acids such as aspartic acid, taurine and glutamine. Methods: We used in vitro electrophysiological recording technique to estimate the effects of glutamine, an amino acid and precursor of neurotransmitters glutamate and GABA, on hippocampal sharp wave ripple activity (SPW-R) in rats. We evoked SPW-Rs in hippocampal slices applying high frequency stimulation. Results: We found that glutamine significantly enhanced the incidence and amplitude of sharp wave ripples. However, duration of sharp wave and ripples’ frequency did not change significantly. It is interesting that glutamine neither prolonged sharp wave ripple activity nor transformed these into pathological events such as recurrent epileptiform discharges. Conclusion: Our data indicate that addition of glutamine in aCSF may optimize the experimental conditions for in vitro electrophysiology without disturbing excitatory – inhibitory balance. This study may provide a better experimental paradigm for exploring the underlying mechanisms of neurological disorders and for searching new therapeutic options to cure these neurological conditions.Keywords: Hippocampus; SPW-Rs; Glutamine; CA3; CA1
Squire LR. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psycholo Rev 1992;99(2):195–231.
Buzsáki G. The hippocampo-neocortical dialogue. Cereb Cortex 1996;6(2):81–92.
Wiltgen BJ, Brown RA, Talton LE, Silva AJ. New circuits for old memories: the role of the neocortex in consolidation. Neuron 2004;44(1):101–8.
BuzsÁk G. Memory consolidation during sleep: a neurophysiological perspective. J Sleep Res 1998;7(Suppl 1):17–23.
Buzsáki G, Leung LW, Vanderwolf CH. Cellular bases of hippocampal EEG in the behaving rat. Brain Res 1983;287(2):139–71.
Bragin A, Jandó G, Nádasdy Z, Hetke J, Wise K, Buzsáki G. Gamma (40-100 Hz) oscillation in the hippocampus of the behaving rat. J Neurosci 1995;15(1 Pt 1):47–60.
Buzsáki G. Two-stage model of memory trace formation: a role for “noisy” brain states. Neuroscience 1989;31(3):551–70.
Hasselmo ME. Neuromodulation: acetylcholine and memory consolidation. Trends Cogn Sci 1999;3(9):351–9.
Buzsáki G, Logothetis N, Singer W. Scaling brain size, keeping timing: evolutionary preservation of brain rhythms. Neuron 2013;80(3):751–64.
Jacobs J, Miller J, Lee SA, Coffey T, Watrous AJ, Sperling MR, et al. Direct Electrical Stimulation of the Human Entorhinal Region and Hippocampus Impairs Memory. Neuron 2016;92(5):983–90.
Maier N, Güldenagel M, Söhl G, Siegmund H, Willecke K, Draguhn A. Reduction of high‐frequency network oscillations (ripples) and pathological network discharges in hippocampal slices from connexin 36‐deficient mice. J Physiol 2002;541(Pt 2):521–8.
Behrens CJ, van den Boom LP, de Hoz L, Friedman A, Heinemann U. Induction of sharp wave–ripple complexes in vitro and reorganization of hippocampal networks. Nat Neurosci 2005;8(11):1560–7.
Collingridge GL, Kehl SJ, McLennan HT. Excitatory amino acids in synaptic transmission in the Schaffer collateral‐commissural pathway of the rat hippocampus. J Physiol 1983;334(1):33–46.
Fonnum F. Glutamate: a neurotransmitter in mammalian brain. J Neurochem 1984;42(1):1–11.
Ul Haq R, Liotta A, Kovacs R, Rösler A, Jarosch MJ, Heinemann U, et al. Adrenergic modulation of sharp wave‐ripple activity in rat hippocampal slices. Hippocampus 2012;22(3):516–33.
Hollnagel JO, Maslarova A, ul Haq R, Heinemann U. GABA B receptor dependent modulation of sharp wave-ripple complexes in the rat hippocampus in vitro. Neurosci Lett 2014;574:15–20.
Dickinson JC, Hamilton PB. The free amino acids of human spinal fluid determined by ion exchange chromatography. J Neurochem 1966;13(11):1179–87.
Hertz L. Functional interactions between neurons and astrocytes I. Turnover and metabolism of putative amino acid transmitters. Prog Neurobiol 1979;13(3):277–323.
Hertz L, Dringen R, Schousboe A, Robinson SR. Astrocytes: glutamate producers for neurons. J Neurosci Res 1999;57(4):417–28.
Dolphin AC, Errington ML, Bliss TV. Long-term potentiation of the perforant path in vivo is associated with increased glutamate release. Nature 1982;297(5866):496–8.
Richter-Levin G, Errington ML, Maegawa H, Bliss TV. Activation of metabotropic glutamate receptors is necessary for long-term potentiation in the dentate gyrus and for spatial learning. Neuropharmacology 1994;33(7):853–7.
Bliss TV, Gardner-Medwin A. Long-lasting potentiation of synaptic transmission in the dentate area of the unanaesthetized rabbit following stimulation of the perforant path. J Physiol 1973;232(2):357–74.
Morris R, Anderson E, Lynch GS, Baudry M. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP 5. Nature 1986;319(6056):774–6.
Bortolotto ZA, Collingridge GL. Characterisation of LTP induced by the activation of glutamate metabotropic receptors in area CA1 of the hippocampus. Neuropharmacology 1993;32(1):1–9.
Gibbs ME, O'dowd BS, Hertz L, Robinson SR, Sedman GL, Ng KT. Inhibition of glutamine synthetase activity prevents memory consolidation. Brain Res Cogn Brain Res 1996;4(1):57–64.
Nimmrich V, Maier N, Schmitz D, Draguhn A. Induced sharp wave‐ripple complexes in the absence of synaptic inhibition in mouse hippocampal slices. J Physiol 2005;563(Pt 3):663–70.
Behrens CJ, Van Den Boom LP, Heinemann U. Effects of the GABAA receptor antagonists bicuculline and gabazine on stimulus‐induced sharp wave‐ripple complexes in adult rat hippocampus in vitro. Eur J Neurosci 2007;25(7):2170–81.
Liotta A, Caliskan G, ul Haq R, Hollnagel JO, Rösler A, Heinemann U, et al. Partial disinhibition is required for transition of stimulus-induced sharp wave-ripple complexes into recurrent epileptiform discharges in rat hippocampal slices. J Neurophysiol 2011;105(1):172–87.