Acute alcohol blocks neurosteroid modulation of synaptic transmission and long-term potentiation in the rat hippocampal slice

Randall, Robert D.; Lee, S.Y.; Jh, Meyer; Wittenberg, George F.; Gruol, Donna L.

doi:10.1016/0006-8993(95)01007-9

Cited by 31 publications

(19 citation statements)

References 52 publications

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“…Dehydroepiandrosterone also facilitated NMDA signalling and enhanced LTP in the hippocampus [157,158]. Further, inhibition of the synthesis of the two latter neurosteroids reduced both NMDA receptor activity and LTP induction in the hippocampus, supporting the view that these steroids are continuously synthesized under physiological conditions and are required for normal synaptic transmission and plasticity [159].…”

Section: Modulation Of Nmda Receptors By Neurosteroidssupporting

confidence: 48%

Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems

Köles

Kató

Hanuska

et al. 2015

Purinergic Signalling

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Glutamate is the main excitatory neurotransmitter of the central nervous system (CNS), released both from neurons and glial cells. Acting via ionotropic (NMDA, AMPA, kainate) and metabotropic glutamate receptors, it is critically involved in essential regulatory functions. Disturbances of glutamatergic neurotransmission can be detected in cognitive and neurodegenerative disorders. This paper summarizes the present knowledge on the modulation of glutamate-mediated responses in the CNS. Emphasis will be put on NMDA receptor channels, which are essential executive and integrative elements of the glutamatergic system. This receptor is crucial for proper functioning of neuronal circuits; its hypofunction or overactivation can result in neuronal disturbances and neurotoxicity. Somewhat surprisingly, NMDA receptors are not widely targeted by pharmacotherapy in clinics; their robust activation or inhibition seems to be desirable only in exceptional cases. However, their fine-tuning might provide a promising manipulation to optimize the activity of the glutamatergic system and to restore proper CNS function. This orchestration utilizes several neuromodulators. Besides the classical ones such as dopamine, novel candidates emerged in the last two decades. The purinergic system is a promising possibility to optimize the activity of the glutamatergic system. It exerts not only direct and indirect influences on NMDA receptors but, by modulating glutamatergic transmission, also plays an important role in glia-neuron communication. These purinergic functions will be illustrated mostly by depicting the modulatory role of the purinergic system on glutamatergic transmission in the prefrontal cortex, a CNS area important for attention, memory and learning.

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Section: Modulation Of Nmda Receptors By Neurosteroidssupporting

confidence: 48%

Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems

Köles

Kató

Hanuska

et al. 2015

Purinergic Signalling

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“…6C). Previous studies have reported LTP depression by acute ethanol treatment at the same low intoxicating concentrations used here (i.e., 33 mM; Blitzer et al, 1990;Randall et al, 1995); however, an ethanol-tolerant form of LTP mediated by intracellular Ca 21 release has also been described at CA1 synapses in response to acute incremental administration of ethanol in vitro (60 mM; Tokuda et al, 2007). Together with these studies, our findings point to the existence of multiple pathways of hippocampal LTP that differ in sensitivity to acute and chronic ethanol actions.…”

Section: Discussionmentioning

confidence: 96%

Emergence of NMDAR‐independent long‐term potentiation at hippocampal CA1 synapses following early adolescent exposure to chronic intermittent ethanol: Role for sigma‐receptors

Sabeti

Gruol

2007

Hippocampus

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Adolescent humans who abuse alcohol are more vulnerable than adults to the development of memory impairments. Memory impairments often involve modifications in the ability of hippocampal neurons to establish long-term potentiation (LTP) of excitatory neurotransmission; however, few studies have examined how chronic ethanol exposure during adolescence affects LTP mechanisms in hippocampus. We investigated changes in LTP mechanisms in hippocamal slices from rats exposed to intoxicating concentrations of chronic intermittent ethanol (CIE) vapors in their period of early-adolescent (i.e., prepubescent) or late-adolescent (i.e., postpubescent) development. LTP was evaluated at excitatory CA1 synapses in hippocampal slices at 24 h after the cessation of air (control) or CIE vapor treatments. CA1 synapses in control slices showed steady LTP following induction by high-frequency stimulation, which was fully dependent on NMDAR function. By contrast, slices from early-adolescent CIE exposed animals showed a compound form of LTP consisting of an NMDAR-dependent component and a slow-developing component independent of NMDARs. These components summated to yield LTP of robust magnitude above LTP levels in age-matched control slices. Bath-application of the sigma-receptor antagonist BD1047 and the neuroactive steroid pregnenolone sulfate, but not acute ethanol application, blocked NMDAR-independent LTP, while leaving NMDAR-dependent LTP intact. Analysis of presynaptic function during NMDAR-independent LTP induction demonstrated increased presynaptic function via a sigma-receptor-dependent mechanism in slices from early-adolescent CIE-exposed animals. By contrast, CIE exposure after puberty onset in late-adolescent animals produced decrements in LTP levels. The identification of a role for sigma-receptors and neuroactive steroids in the development of NMDAR-independent LTP suggests an important pathway by which hippocampal synaptic plasticity, and perhaps memory, may be uniquely altered by chronic ethanol exposure during the prepubescent phase of adolescent development.

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“…Several neuroactive steroids (McEwen, 1994;Randall et al, 1995;Diamond et al, 1996;Foy, 2001;Dubrovsky, 2005;Krugers et al, 2005), including PREGS (Sliwinski et al, 2004), have been shown to inhibit or augment hippocampal LTP. Such actions are consistent with a role for LTP in the memory/mood-altering effects of PREGS.…”

Section: Introductionmentioning

confidence: 99%

Steroid pregnenolone sulfate enhances NMDA‐receptor‐independent long‐term potentiation at hippocampal CA1 synapses: Role for L‐type calcium channels and sigma‐receptors

et al. 2007

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Severe stress elevates plasma and CNS levels of endogenous neuroactive steroids that can contribute to the influence of stress on memory formation. Among the neuroactive steroids, pregnenolone sulfate (PREGS) reportedly strengthens memories and is readily available as a memory-enhancing supplement. PREGS actions on memory may reflect its ability to produce changes in memory-related neuronal circuits, such as long-term potentiation (LTP) of excitatory transmission in hippocampus. Here, we report a previously undiscovered pathway by which PREGS exposure promotes activity-dependent LTP of field excitatory postsynaptic potentials at CA1 synapses in hippocampal slices. Thus, application of PREGS, but not the phosphated conjugate of the steroid, selectively facilitates the induction of a slow-developing LTP in response to high-frequency (100 Hz) afferent stimulation, which is not induced in the absence of the steroid. The slow-developing LTP is independent of NMDA-receptor function (i.e., dAP5 insensitive) but dependent on functional L-type voltage-gated calcium channels (VGCC) and sigma-receptors. By contrast, PREGS at the highest concentration tested produces a depression in NMDA-receptor-dependent LTP, which is evident when sigma-receptor function is compromised by the presence of a sigma-receptor antagonist. We found that at early times during the induction phase of L-type VGCC-dependent LTP, PREGS via sigma-receptors transiently enhances presynaptic function. As well, during the maintenance phase of L-type VGCC-dependent LTP, PREGS promotes a further increase in presynaptic function downstream of LTP induction, as evidenced by a decrease in paired-pulse facilitation. The identification of complex regulatory actions of PREGS on LTP, involving sigma-receptors, L-type VGCCs, NMDA-receptors, and inhibitory circuits will aid future research endeavors aimed at understanding the precise mechanisms by which this stress-associated steroid may engage multiple LTP-signaling pathways that alter synaptic transmission at memory-related synapses.

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Acute alcohol blocks neurosteroid modulation of synaptic transmission and long-term potentiation in the rat hippocampal slice

Cited by 31 publications

References 52 publications

Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems

Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems

Emergence of NMDAR‐independent long‐term potentiation at hippocampal CA1 synapses following early adolescent exposure to chronic intermittent ethanol: Role for sigma‐receptors

Steroid pregnenolone sulfate enhances NMDA‐receptor‐independent long‐term potentiation at hippocampal CA1 synapses: Role for L‐type calcium channels and sigma‐receptors

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