Brain lactic acidosis and synaptic function

1990 ◽  
Vol 68 (2) ◽  
pp. 164-169 ◽  
Author(s):  
Wolfgang Walz ◽  
Diane E. Harold
Keyword(s):  
Lactic Acid ◽  
Synaptic Transmission ◽  
Hippocampal Slices ◽  
Sodium Lactate ◽  
Extracellular Ph ◽  
Synaptic Function ◽  
Excitatory Postsynaptic Potential ◽  
Irreversible Damage ◽  
Acid Release ◽  
Neuronal Transmission

Measurements of the presynaptic fiber volley (PSFV), the population excitatory postsynaptic potential (EPSP), and the extracellular pH in the dendritic CA1 layer of rat hippocampal slices were used to evaluate the effects of lactacidosis on central synaptic transmission. Replacement of NaCl with sodium lactate (up to 30 mM) was found not to affect the PSFV; however, the EPSP was reversibly suppressed. Sodium citrate, with added CaCl2 to adjust for Ca2+ chelation, had the same effect as sodium lactate. Addition of lactic acid influenced the PSFV only when, at a concentration of 30 mM, the extracellular pH dropped to 6.6 or lower. With lactic acid concentrations of up to 20 mM, which produced pH levels of 6.8 in the slice, effects on the EPSP were reversible. However, 30 mM lactic acid suppressed both the PSFV and EPSP irreversibly. These results show that synaptic transmission is much more susceptible to lactacidosis than presynaptic axonal transmission. They also show that high levels of lactate, albeit causing suppression of synaptic transmission, do not cause irreversible damage. However, acidosis associated with lactic acid release may damage synaptic transmission irreversibly.Key words: acidosis, hippocampal slice, ischemia, lactate, lactic acid, neuronal transmission, synapse.

Functional Characterization of Des-IGF-1 Action at Excitatory Synapses in the CA1 Region of Rat Hippocampus

2005 ◽  
Vol 94 (1) ◽  
pp. 247-254 ◽  
Author(s):  
Melinda M. Ramsey ◽  
Michelle M. Adams ◽  
Olusegun J. Ariwodola ◽  
William E. Sonntag ◽  
Jeff L. Weiner
Keyword(s):  
Synaptic Transmission ◽  
Hippocampal Slices ◽  
Functional Characterization ◽  
Excitatory Postsynaptic Potential ◽  
Excitatory Synapses ◽  
Aged Rats ◽  
Cognitive Improvement ◽  
Ca1 Region

Insulin-like growth factor-1 (IGF-1) and growth hormone play a major role in the growth and development of tissues throughout the mammalian body. Plasma IGF-1 concentrations peak during puberty and decline with age. We have determined that chronic treatments to restore plasma IGF-1 concentrations to adult levels attenuate spatial learning deficits in aged rats, but little is known of the acute actions of IGF-1 in the brain. To this end, we utilized hippocampal slices from young Sprague-Dawley rats to characterize the acute effects of des-IGF-1 on excitatory synaptic transmission in the CA1 region. We observed a 40% increase in field excitatory postsynaptic potential (fEPSP) slope with application of des-IGF-1 (40 ng/ml) and used whole cell patch-clamp recordings to determine that this enhancement was due to a postsynaptic mechanism involving α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) but not N-methyl-d-aspartate receptors. Furthermore, the enhancement was completely blocked by the broad-spectrum tyrosine kinase inhibitor, genistein (220 μM), and significantly reduced by the PI3K blockers wortmannin (1 μM) and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (10 μM), suggesting that the effect was predominantly dependent on PI3K activation. This characterization of the acute actions of des-IGF-1 at hippocampal excitatory synapses may provide insight into the mechanism by which long-term increases in plasma IGF-1 impart cognitive benefits in aged rats. Increases in AMPA receptor-mediated synaptic transmission may contribute directly to cognitive improvement or initiate long-term changes in synthesis of proteins such as brain-derived neurotrophic factor that are important to learning and memory.

Enhanced Synaptic Transmission in CA1 Hippocampus After Eyeblink Conditioning

1997 ◽  
Vol 78 (2) ◽  
pp. 1184-1187 ◽  
Author(s):  
John M. Power ◽  
Lucien T. Thompson ◽  
James R. Moyer ◽  
John F. Disterhoft
Keyword(s):  
Synaptic Transmission ◽  
Repeated Measures ◽  
Eyeblink Conditioning ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Trace Conditioning ◽  
Excitatory Postsynaptic Potential ◽  
Field Potentials ◽  
Repeated Measures Analysis ◽  
Conditioned Responses

Power, John M., Lucien T. Thompson, James R. Moyer, Jr., and John F. Disterhoft. Enhanced synaptic transmission in CA1 hippocampus after eyeblink conditioning. J. Neurophysiol. 78: 1184–1187, 1997. CA1 field potentials evoked by Schaffer collateral stimulation of hippocampal slices from trace-conditioned rabbits were compared with those from naive and pseudoconditioned controls. Conditioned rabbits received 80 trace conditioning trials daily until reaching a criterion of 80% conditioned responses in a session. Hippocampal slices were prepared 1 or 24 h after reaching criterion (for trace-conditioned animals) or after a final unpaired stimulus session (for pseudoconditioned animals); naive animals were untrained. Both somatic and dendritic field potentials were recorded in response to various stimulus durations. Recording and data reduction were performed blind to the conditioning state of the rabbit. The excitatory postsynaptic potential slope was greater in slices prepared from trace-conditioned animals killed 1 h after conditioning than in naive and pseudoconditioned controls (repeated-measures analysis of variance, F = 4.250, P < 0.05). Associative learning specifically enhanced synaptic transmission between CA3 and CA1 immediately after training. This effect was not evident in the population field potential measured 24 h later.

scholarly journals Early low-level developmental arsenic exposure impacts mouse hippocampal synaptic function

2021 ◽  
Author(s):  
Karl F Foley ◽  
Daniel Barnett ◽  
Deborah A Cory-Slechta ◽  
Houhui Xia
Keyword(s):  
Synaptic Transmission ◽  
Hippocampal Slices ◽  
Arsenic Exposure ◽  
Long Term Potentiation ◽  
Epidemiological Studies ◽  
Synaptic Function ◽  
Learning Deficits ◽  
Term Potentiation ◽  
The Impact

Background: Arsenic is a well-established carcinogen known to increase all-cause mortality, but its effects on the central nervous system are less well understood. Recent epidemiological studies suggest that early life exposure to arsenic is associated with learning deficits and behavioral changes, and increased arsenic exposure continues to affect an estimated 200 million individuals worldwide. Previous studies on arsenic exposure and synaptic function have demonstrated a decrease in synaptic transmission and long-term potentiation in adult rodents, but have relied on in vitro or extended exposure in adulthood. Therefore, little is known about the effect of arsenic exposure in development. Objective: Here, we studied the effects of gestational and early developmental arsenic exposure in juvenile mice. Specifically, our objective was to investigate the impact of arsenic exposure on synaptic transmission and plasticity in the hippocampus. Methods: C57BL/6 females were exposed to arsenic (0, 50ppb, 36ppm) in their drinking water two weeks prior to mating and continued to be exposed to arsenic throughout gestation and after parturition. We then performed field recordings in acute hippocampal slices from the juvenile offspring prior to weaning (P17-P23). In this paradigm, the juvenile mice are only exposed to arsenic in utero and via the mothers milk. Results: High (36ppm) and relatively low (50ppb) arsenic exposure both lead to decreased basal synaptic transmission in the hippocampus of juvenile mice. There was a mild decrease in paired-pulse facilitation in juvenile mice exposed to high, but not low, arsenic, suggesting the alterations in synaptic transmission are primarily post-synaptic. Finally, high developmental arsenic exposure led to a significant increase in long-term potentiation. Discussion: These results suggest that indirect, ecologically-relevant arsenic exposure in early development impacts hippocampal synaptic transmission and plasticity that could underlie learning deficits reported in epidemiological studies.

A novel cholinergic induction of long-term potentiation in rat hippocampus

1994 ◽  
Vol 72 (4) ◽  
pp. 2034-2040 ◽  
Author(s):  
J. M. Auerbach ◽  
M. Segal
Keyword(s):  
Synaptic Transmission ◽  
Hippocampal Slices ◽  
Extracellular Recording ◽  
Long Term Potentiation ◽  
Common Mechanism ◽  
Excitatory Postsynaptic Potential ◽  
Tetanic Stimulation ◽  
Term Potentiation ◽  
Bath Application

1. We studied long-term cholinergic effects on synaptic transmission in submerged hippocampal slices using intra- and extracellular recording techniques. 2. Bath application of submicromolar concentrations of carbachol (CCh) produced a gradually developing, long-lasting increase in the CA1 excitatory postsynaptic potential and population spike. This potentiation was blocked by atropine and, hence, named muscarinic long-term potentiation (LTPm). Application of DL-2-amino-5-phosphonovaleric acid had no effect on LTPm, indicating that this phenomenon is N-methyl-D-aspartate receptor independent. 3. These effects of CCh were not likely to be due to the blockade of one of several K+ conductances by the drug; the time and concentration dependence of LTPm were different from those associated with cholinergic blockade of K+ conductances. 4. Removal of extracellular calcium (Cao2+) from the bath blocked synaptic transmission. CCh added in calcium-free medium induced LTPm, which was revealed upon removal of the drug by washing with normal calcium-containing medium. Neither cutting CA1-CA3 connections nor cessation of synaptic stimulation interfered with LTPm induction. 5. Application of thapsigargin or H-7 together with CCh blocked LTPm, suggesting the involvement of intracellular calcium (Cai2+) stores and protein kinases, respectively, in the LTPm mechanism. 6. Subthreshold cholinergic stimulation coupled with subthreshold tetanic stimulation caused LTP. CCh had no effect when administered after the LTP mechanism had been saturated by repeated suprathreshold tetani. Tetanic stimulation failed to cause LTP when applied after LTPm had been induced by CCh. These experiments indicate that tetanus-induced potentiation and LTPm share a common mechanism and provide a direct link between ACh and mechanisms of synaptic plasticity.

scholarly journals Developmental synaptic regulator, TWEAK/Fn14 signaling, is a determinant of synaptic function in models of stroke and neurodegeneration

2021 ◽  
Vol 118 (6) ◽  
pp. e2001679118
Author(s):  
Dávid Nagy ◽  
Katelin A. Ennis ◽  
Ru Wei ◽  
Susan C. Su ◽  
Christopher A. Hinckley ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Neural Circuit ◽  
Hippocampal Slices ◽  
Visual Development ◽  
Synaptic Function ◽  
Synaptic Physiology ◽  
Mature Brain ◽  
Circuit Development ◽  
Basal Synaptic Transmission

Identifying molecular mediators of neural circuit development and/or function that contribute to circuit dysfunction when aberrantly reengaged in neurological disorders is of high importance. The role of the TWEAK/Fn14 pathway, which was recently reported to be a microglial/neuronal axis mediating synaptic refinement in experience-dependent visual development, has not been explored in synaptic function within the mature central nervous system. By combining electrophysiological and phosphoproteomic approaches, we show that TWEAK acutely dampens basal synaptic transmission and plasticity through neuronal Fn14 and impacts the phosphorylation state of pre- and postsynaptic proteins in adult mouse hippocampal slices. Importantly, this is relevant in two models featuring synaptic deficits. Blocking TWEAK/Fn14 signaling augments synaptic function in hippocampal slices from amyloid-beta–overexpressing mice. After stroke, genetic or pharmacological inhibition of TWEAK/Fn14 signaling augments basal synaptic transmission and normalizes plasticity. Our data support a glial/neuronal axis that critically modifies synaptic physiology and pathophysiology in different contexts in the mature brain and may be a therapeutic target for improving neurophysiological outcomes.

NMDA-Independent LTP by Adenosine A2 Receptor-Mediated Postsynaptic AMPA Potentiation in Hippocampus

1997 ◽  
Vol 78 (4) ◽  
pp. 1965-1972 ◽  
Author(s):  
Kofi Kessey ◽  
David J. Mogul
Keyword(s):  
Synaptic Transmission ◽  
Ampa Receptor ◽  
Hippocampal Slices ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Common Mechanism ◽  
Excitatory Postsynaptic Potential ◽  
Ca1 Region ◽  
The Brain

Kessey, Kofi and David J. Mogul. NMDA-independent LTP by adenosine A2 receptor-mediated postsynaptic AMPA potentiation in hippocampus. J. Neurophysiol. 78: 1965–1972, 1997. The role of adenosine A2 receptors in normal synaptic transmission and tetanus-induced long-term potentiation (LTP) was tested by stimulation of the Schaffer collateral pathway and recording of the field excitatory postsynaptic potential (EPSP) in the CA1 region of rat transverse hippocampal slices. Activation of adenosine A2 receptors with the A2 agonist N 6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA; 20 nM) enhanced synaptic transmission during low-frequency test pulses (0.033 Hz). Paired stimulation before and during DPMA exposure indicated no paired-pulse facilitation as a result of A2 activation, suggesting that enhancement was not a result of presynaptic modulation. DPMA enhanced the early phase α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) component of the EPSP. In contrast, DPMA had no effect on the N-methyl-d-aspartate (NMDA) component isolated using low extracellular Mg2+ and the AMPA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM), indicating that the effects of A2 activation on synaptic transmission were mediated by a postsynaptic enhancement of the AMPA response. Activation of adenosine A2 receptors during a brief tetanus (100 Hz, 1 s) increased the level of LTP by 36% over that seen in response to a tetanus under control conditions. DPMA exposure after prior induction of LTP showed no additional potentiation, indicating that the mechanisms that contribute to both types of increases in synaptic transmission share a common mechanism. A slow onset NMDA-independent LTP could be induced by application of a tetanus during perfusion of DPMA with the NMDA blocker AP5 (50 μM). Blockade of L-type Ca channels with nifedipine (10 μM) had no effect on normal synaptic transmission but reduced NMDA-independent LTP by 32%. Very little NMDA-independent LTP could be induced after prior saturation of NMDA-dependent LTP via multiple tetani spaced 10 min apart, indicating that both forms of LTP are eventually convergent on a common mechanism, presumably the postsynaptic AMPA receptor response. Because extracellular adenosine levels are modulated by cellular activity throughout the brain and because adenosine receptor activation can markedly alter levels of synaptic transmission independent of NMDA receptors, adenosine may play an important and complex role as a modulator of synaptic transmission in the brain.

scholarly journals Hyperoxic stimulation of synchronous orthodromic activity and induction of neural plasticity does not require changes in excitatory synaptic transmission

2010 ◽  
Vol 109 (3) ◽  
pp. 820-829 ◽  
Author(s):  
Alfredo J. Garcia ◽  
Robert W. Putnam ◽  
Jay B. Dean
Keyword(s):  
Synaptic Transmission ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Excitatory Synaptic Transmission ◽  
Population Spike ◽  
Excitatory Postsynaptic Potential ◽  
Synaptic Activation ◽  
Ca1 Neurons ◽  
Stimulation Of

The first study, described in the companion article, reports that acute exposure of rat hippocampal slices to either hyperbaric oxygen (HBO: 2.84 and 4.54 atmospheres absolute, ATA) or normobaric reoxygenation (NBOreox; i.e., normobaric hyperoxia: 0.6 or 0.0 → 0.95 ATA) stimulates synchronous orthodromic activity in CA1 neurons, which includes activation of O2-induced potentiation (OxIP) and, in some cases, hyperexcitability (secondary population spikes, sPS). In this second study we tested the hypothesis that HBO and NBOreox increase orthodromic activity of CA1 neurons (oPS, orthodromic population spike) and OxIP via a combination of both increased excitatory synaptic transmission (field excitatory postsynaptic potential, fEPSP) and intrinsic excitability (antidromic population spike, aPS). HBO and NBOreox increased the oPS but rarely increased or potentiated the fEPSP. HBO exposure produced epileptiform antidromic activity, which was abolished during inhibition of fast GABAergic and glutamatergic synaptic transmission. Decreasing O2 from 0.95 ATA (control) to 0.6 ATA (intermediate O2) or 0.0 ATA (hypoxia) reversibly abolished the fEPSP, and reoxygenation rarely induced potentiation of the fEPSP or aPS. Intracellular recordings and antidromic field potential recordings, however, revealed that synaptic transmission and neuronal excitability were preserved, albeit at lower levels, in 0.60 ATA O2. Together, these data indicate that 1) the changes in excitatory postsynaptic activity are not required for stimulation of the oPS during and HBO/NBOreox or for activation of OxIP, suggesting the latter is a form of intrinsic plasticity; 2) HBO disinhibits spontaneous synaptic transmission to induce epileptiform activity; and 3) although synchronous synaptic activation of the CA1 neuronal population requires hyperoxia (i.e., 0.95 ATA O2), synaptic activation of individual CA1 neurons does not.

scholarly journals Intracellular Acidification Causes Adenosine Release During States of Hyperexcitability in the Hippocampus

2009 ◽  
Vol 102 (3) ◽  
pp. 1984-1993 ◽  
Author(s):  
Chris G. Dulla ◽  
Bruno G. Frenguelli ◽  
Kevin J. Staley ◽  
Susan A. Masino
Keyword(s):  
Synaptic Transmission ◽  
Intracellular Ph ◽  
Hippocampal Slice ◽  
Dominant Role ◽  
Hippocampal Slices ◽  
Extracellular Ph ◽  
Ph Change ◽  
Extracellular Adenosine ◽  
Adenosine Concentration

Decreased pH increases extracellular adenosine in CNS regions as diverse as hippocampus and ventral medulla. However, thus far there is no clear consensus whether the critical pH change is a decrease in intracellular and/or extracellular pH. Previously we showed that a decrease in extracellular pH is necessary and a decrease in intracellular pH alone is not sufficient, to increase extracellular adenosine in an acute hippocampal slice preparation. Here we explored further the role of intracellular pH under different synaptic conditions in the hippocampal slice. When synaptic excitability was increased, either during γ-aminobutyric acid type A receptor blockade in CA1 or after the induction of persistent bursting in CA3, a decrease in intracellular pH alone was now sufficient to: 1) elevate extracellular adenosine concentration, 2) activate adenosine A1 receptors, 3) decrease excitatory synaptic transmission (CA1), and 4) attenuate burst frequency in an in vitro seizure model (CA3). Hippocampal slices obtained from adenosine A1 receptor knockout mice did not exhibit these pH-mediated effects on synaptic transmission, further confirming the role of adenosine acting at the adenosine A1 receptor. Taken together, these data strengthen and add significantly to the evidence outlining a change in pH as an important stimulus influencing extracellular adenosine. In addition, we identify conditions under which intracellular pH plays a dominant role in regulating extracellular adenosine concentrations.

Protective Effect of High Glucose Against Ischemia-Induced Synaptic Transmission Damage in Rat Hippocampal Slices

2002 ◽  
Vol 88 (1) ◽  
pp. 236-248 ◽  
Author(s):  
Guo-Feng Tian ◽  
Andrew J. Baker
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Cell ◽  
High Glucose ◽  
Glucose Concentration ◽  
Cell Layer ◽  
Hippocampal Slices ◽  
Excitatory Postsynaptic Potential ◽  
Pyramidal Cell Layer ◽  
Before And After

Cerebral ischemic damage is an important cause of morbidity and mortality. However, there is conflicting evidence regarding the effect of the extracellular glucose concentration in focal and global ischemic injury. This study was designed to investigate this effect in ischemia-induced synaptic transmission damage in rat hippocampal slices. Slices were superfused with artificial cerebrospinal fluid (ACSF) containing various concentrations of glucose before and after ischemia. The evoked somatic postsynaptic population spike (PS) and dendritic field excitatory postsynaptic potential (fEPSP) were extracellularly recorded in the CA1 stratum pyramidal cell layer and s. radiatum after stimulation of the Schaeffer collaterals, respectively. The glucose concentration in ACSF before and after ischemia determined the duration of ischemia tolerated by synaptic transmission as demonstrated by complete recovery of the somatic PS and dendritic fEPSP. Specifically, the somatic PS and dendritic fEPSP completely recovered following 3, 4, and 5 min of ischemia only when slices were superfused with ACSF containing 4, 10, and 20 mM glucose before and after ischemia, respectively. The latencies of the somatic and dendritic ischemic depolarization (ID) occurrence in the CA1 s. pyramidal cell layer and s. radiatum were significantly longer with 10 than 4 mM glucose in ACSF before ischemia and significantly longer with 20 than 10 mM glucose in ACSF before ischemia. Regardless of the glucose concentration in ACSF before and after ischemia, the somatic PS and dendritic fEPSP only partially recovered when ischemia was terminated at the occurrence of ID. These results indicate that high glucose in ACSF during the period before and after ischemia significantly protects CA1 synaptic transmission against in vitro ischemia-induced damage through postponing the occurrence of ID.

scholarly journals Neuromodulation and neuroprotective effects of chlorogenic acids in excitatory synapses of mouse hippocampal slices

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mara Yone D. Fernandes ◽  
Fernando Dobrachinski ◽  
Henrique B. Silva ◽  
João Pedro Lopes ◽  
Francisco Q. Gonçalves ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Molecular Mechanisms ◽  
Hippocampal Slices ◽  
Quinic Acid ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Synaptic Dysfunction ◽  
Chlorogenic Acids ◽  
Coffee Intake

AbstractThe increased healthspan afforded by coffee intake provides novel opportunities to identify new therapeutic strategies. Caffeine has been proposed to afford benefits through adenosine A2A receptors, which can control synaptic dysfunction underlying some brain disease. However, decaffeinated coffee and other main components of coffee such as chlorogenic acids, also attenuate brain dysfunction, although it is unknown if they control synaptic function. We now used electrophysiological recordings in mouse hippocampal slices to test if realistic concentrations of chlorogenic acids directly affect synaptic transmission and plasticity. 3-(3,4-dihydroxycinnamoyl)quinic acid (CA, 1–10 μM) and 5-O-(trans-3,4-dihydroxycinnamoyl)-D-quinic acid (NCA, 1–10 μM) were devoid of effect on synaptic transmission, paired-pulse facilitation or long-term potentiation (LTP) and long-term depression (LTD) in Schaffer collaterals-CA1 pyramidal synapses. However, CA and NCA increased the recovery of synaptic transmission upon re-oxygenation following 7 min of oxygen/glucose deprivation, an in vitro ischemia model. Also, CA and NCA attenuated the shift of LTD into LTP observed in hippocampal slices from animals with hippocampal-dependent memory deterioration after exposure to β-amyloid 1–42 (2 nmol, icv), in the context of Alzheimer’s disease. These findings show that chlorogenic acids do not directly affect synaptic transmission and plasticity but can indirectly affect other cellular targets to correct synaptic dysfunction. Unraveling the molecular mechanisms of action of chlorogenic acids will allow the design of hitherto unrecognized novel neuroprotective strategies.

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