GABA-induced potentiation of neuronal excitability occurs during contiguous pairings with intracellular calcium elevation

doi:10.1016/0006-8993(91)90174-T

Brain Research

Volume 554, Issues 1–2, 19 July 1991, Pages 77-84

https://doi.org/10.1016/0006-8993(91)90174-T Get rights and content

The temporal convergence of neuronal signals is commonly considered as a likely prerequisite for enhanced neuronal excitability underlying the induction of associative memories. Here we report that transmitter application on presynaptic terminals of theHermissenda Type B photoreceptors, when paired with depolarization, results in a potentiation of the excitability of the B-cell which derives from an increase in input resistance across the B-cell soma membrane. Pressure microapplication of γ-aminobutyric acid (GABA) (12.5 μM) on the terminal branches of theHermissenda Type B photoreceptors results in the fast(< 1s) activation of an inward Cl⁻ conductance, characterized by a decrease in neuronal membrane resistance and an accompanying hyperpolarization (3–6 mV) of the B-cell. A slower effect of GABA, characterized by a slight depolarization (2–4 mV) and increase in resistance was observed approximately 2 min after GABA application. Following bath application of the Cl⁻ channel blocker picrotoxin (100 μM), this increase in resistance was observed within 20 s of GABA application, suggesting that it was normally masked by the faster Cl⁻ conductance. The magnitude of the resistance increase in response to GABA was enhanced when the B-cell was held at depolarized membrane potentials (−40 to −20 mV), but was eliminated if Ca²⁺ was removed from the extracellular bath, or if the non-specific protein kinase inhibitor H7 (100 μM) was added to the extracellular bath. In a final experiment, GABA application was paired with a transient (10 s) depolarization of the B-cell (to −20 mV). No initial effect of this pairing (at 30 s) could be detected, although an increase in resistance in the B-cell was observed after 5 min and persisted for at least 10 min. This persistent increase in resistance was not observed in response to GABA application without depolarization or in response to depolarization without GABA application. These findings suggest a mechanism whereby enhanced excitability of single neurons may result from converging neuronal signals (i.e. transmitter application and postsynaptic depolarization), and share many similarities with mechanisms underlying long-term potentiation, particularly like that seen in hippocampal mossy fiber synapses in the mammalian brain.

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In addition, a one-trial in vitro procedure consisting of pairing the CS with mechanical perturbation of the statocyst produces a significant Ca2+-dependent increase in input resistance of sensory neurons (a correlate of enhanced excitability) that is detected within minutes postconditioning.83 Moreover, a one-trial in vitro procedure involving GABA application to the region of the sensory neuron terminal branches (nominal US) paired with a 10-sec depolarization of the sensory neuron (nominal CS) resulted in an increase in the input resistance of the sensory neuron that persisted for at least 10 min.86 These studies indicate that the application of a neurotransmitter when paired with depolarization resulting in a brief period of Ca2+ elevation is sufficient to produce enhanced excitability, and the procedures may engage the essential components for the formation of associations underlying conditioning.
Cellular studies of associative learning indicate that changes in synaptic strength and intrinsic enhanced cellular excitability are basic mechanisms supporting the formation and expression of memory within the nervous system. An analysis of the Pavlovian conditioned CR complex in Hermissenda has led to the identification of molecular mechanisms contributing to the acquisition of short-term, intermediate-term, and long-term memory. Cellular and synaptic changes have been examined at multiple loci within the neural network supporting the generation of the CR complex. The neural circuitry supporting the expression of the conditioned responses has been identified, and this provides for the opportunity to understand how cellular and molecular modifications at different loci within a neural circuit can reconfigure the network to express learned behavior.
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Cellular studies of associative learning suggest that changes in synaptic strength and intrinsic enhanced cellular excitability are basic mechanisms supporting the formation and expression of memory within the nervous system. An analysis of Pavlovian conditioning of Hermissenda has led to the identification of molecular mechanisms contributing to the acquisition of short-term, intermediate-term, and long-term memory. The neural circuitry supporting the expression of the conditioned response has been identified and provides for the opportunity to understand how cellular and molecular modifications at specific loci within a neural circuit can be reconfigured to express learned behavior.
Phospholipases and arachidonic acid contribute independently to sensory transduction and associative neuronal facilitation in Hermissenda type B photoreceptors
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During contiguous pairings of light and rotation, B photoreceptors in the Hermissenda eye undergo an increase in excitability that contributes to a modification of several light-elicited behaviors. This excitability increase requires a light-induced rise in intracellular Ca²⁺ in the photoreceptor concomitant with transmitter binding to G protein-coupled receptors as a result of presynaptic vestibular hair cell stimulation. Phospholipases and arachidonic acid (ArA) are here reported to be involved in independent signal transduction pathways that underlie both receptor function and activity-dependent facilitation of the B photoreceptor. 4-Bromophenacyl bromide (BPB), an inhibitor of phospholipases A₂ (PLA₂) and C (PLC), blocked the generation of light-induced depolarizing generator potentials, but had no affect on the inhibitory postsynaptic potential (IPSP) in the B cell that results from hair cell stimulation. Quinacrine, which predominantly blocks the activity of PLA₂ in neurons, had no affect on either the light response or the IPSP, but did block increases in excitability (i.e. increased input resistance and elicited spike rate) of the B cell that results from pairings of light and presynaptic vestibular stimulation (i.e., in vitro associative conditioning). Neither nordihydroquararetic acid (NDGA), which inhibits metabolism of ArA by cyclooxygenase, nor indomethacin, which inhibits lipoxygenase metabolism of ArA, affected the light response or IPSP, but both blocked the increases in excitability in the B cell that accompanied in vitro conditioning. In combination with earlier results, these data suggest that ArA activates PKC in a synergistic fashion with Ca²⁺ and diacylglycerol in the B cell, and suggest that PLA₂-induced ArA release, though not necessary for transduction of light or the hair cell-induced IPSP in the B cell, is a critical component of the convergence of signals that precipitates associative facilitation in this system. © 1997 Elsevier Science B.V. All rights reserved.
GABA-induced synaptic facilitation at type B to A photoreceptor connections in Hermissenda
1997, Brain Research Bulletin
Gamma-aminobutyric acid (GABA) is a prevalent neurotransmitter in both vertebrate and invertebrate systems. Here we report that, in addition to its usual inhibitory actions, GABA induced synaptic facilitation at type B to A photoreceptor connections of the marine mollusk Hermissenda when applied transiently to the isolated nervous system. Synaptic facilitation also occurred in response to mechanical stimulation of the GABAergic hair cells, which are normally activated by rotational unconditioned stimuli during behavioral training of the intact animal. This synaptic facilitation represents a novel form of GABA-induced neuromodulation which may contribute to learning-dependent suppression of phototaxis in Hermissenda.
Potassium currents in presynaptic hair cells of Hermissenda
1997, Biophysical Journal
Apart from their primary function as balance sensors, Hermissenda hair cells are presynaptic neurons involved in the Ca(2+)-dependent neuronal plasticity in postsynaptic B photoreceptors that accompanies classical conditioning. With a view to beginning to understand presynaptic mechanisms of plasticity in the vestibulo-visual system, a locus for conditioning-induced neuronal plasticity, outward currents that may govern the excitability of hair cells were recorded by means of a whole-cell patch-clamp technique. Three K+ currents were characterized: a 4-aminopyridine-sensitive transient outward K+ current (IA), a tetraethyl ammonium-sensitive delayed rectifier K+ current (IK,V), and a Ca(2+)-activated K+ current (IK,Ca). IA activates and decays rapidly; the steady-state activation and inactivation curves of the current reveal a window current close to the apparent resting voltage of the hair cells, suggesting that the current is partially activated at rest. By modulating firing frequency and perhaps damping membrane oscillations, IA may regulate synaptic release at baseline. In contrast, IK,V and IK,Ca have slow onset and exhibit little or no inactivation. These two K+ currents may determine the duration of the repolarization phase of hair-cell action potentials and hence synaptic release via Ca2+ influx through voltage-gated Ca2+ channels. In addition, IK,Ca may be responsible for the afterhyperpolarization of hair cell membrane voltage following prolonged stimulation.
The effects of methylmercury on endogenous dopamine efflux from mouse striatal slices
1996, Toxicology Letters
The present study investigated the effects of in vitro methylmercury (MeHg) exposure on endogenous dopamine (DA) efflux from mouse striatal slices. MeHg produced a concentration-dependent increase in the spontaneous efflux of DA which was independent of the availability of Ca²⁺ in the superfusion medium. The Ca²⁺-dependent K⁺-evoked release of DA was significantly enhanced by 50 and 100 μM MeHg. This increase could not be solely accounted for by the MeHg-induced increase in spontaneous DA efflux. The K⁺-stimulated efflux of DA was enhanced by MeHg m both the presence and absence of Ca²⁺in the superfusion medium, suggesting that under depolarizing conditions, DA efflux induced by MeHg has a Ca²⁺-independent component. The alterations in DA efflux occurred at concentrations of MeHg previously found in the CNS of animals exhibiting symptoms of MeHg intoxication suggesting that alterations in DA neurotransmission in the striatum may contribute to the symptoms of MeHg toxicity.

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GABA-induced potentiation of neuronal excitability occurs during contiguous pairings with intracellular calcium elevation

Biophys. J.

Behav. Neural. Biol.

Neurosci. Lett.

Biophys. J.

Trends Neurosci.

Neuron

Brain Res. Bull.

Behav. Brain Res.

Eur. J. Pharmacol.

Membrane depolarization accumulates during acquisition of an associative behavioral change

Science

Regulation ofHermissenda K+ channels by cytoplasmic and membrane-associated C-kinase

J. Neurochem.

Electrophysiology of GABAA and GABAB receptor subtypes

Trends Neurosci.

Phospholipase A2 and phospholipase C are activated by distinct GTP binding proteins in response to alpha-1-adrenergic stimulation in FRTL5 thyroid cells

GABAA receptor function is regulated by phosphorylation in acutely dissociated guinea pig hippocampal neurones

J. Physiol.

Light- and voltage-dependent increases of calcium ion concentration in molluscan photoreceptors

J. Neurophysiol.

Regulation ofHermissenda K⁺ channels by cytoplasmic and membrane-associated C-kinase

Electrophysiology of GABA_A and GABA_B receptor subtypes

Phospholipase A₂ and phospholipase C are activated by distinct GTP binding proteins in response to alpha-1-adrenergic stimulation in FRTL5 thyroid cells

GABA_A receptor function is regulated by phosphorylation in acutely dissociated guinea pig hippocampal neurones