Long-term synaptic transformation of hippocampal CA1 gamma-aminobutyric acid synapses and the effect of anandamide.

Abstract

Evidence is presented for a distinctive type of hippocampal synaptic modification [previously described for a molluscan y-aminobutyric acid (GABA) synapse after paired pre-and postsynaptic excitation]: transformation of GABA-mediated synaptic inhibition into synaptic excitation. This transformation persists with no further paired stimulation for 60 min or longer and is termed long-term transformation. Long-term transformation is shown to contribute to pairing-induced long-term potentiation but not to long-term potentiation induced by presynaptic stimulation alone. This synaptic LTT is shown to contribute significantly to pairing-induced LTP but not to tetanus-induced (i.e., not paired with depolarization) LTP. The same synaptic transformation was previously identified for the GABA synapses of the visual-vestibular sensory cells of the snail Hermissenda (4).MATERIALS AND METHODS The slicing procedure has been described (5). In brief, recordings were obtained in 400-,um-thick transverse hippocampal slices of adult (150 g) male Sprague-Dawley rats. Slices were maintained at 34-35°C in a submersion chamber perfused with artificial cerebrospinal fluid (126 mM NaCl/3.0 mM KCl/1.25 mM NaH2PO4/24 mM NaHCO3/2.0 mM MgSO4/2.0 mM CaCl2/10 mM glucose). The flow rate was adjusted to 1.5 ml-min-1 and was bubbled with 95% 02/5% CO2. Intracellular recordings were obtained with micropipettes filled with 1 M KAc/l mM KCl and with a resistance of 60-80 Mfl. Intracellular recordings from the CAl neurons were amplified with an Axoclamp 2A amplifier. Data were digitized at 1-10 KHz and stored in magnetic tape for later analysis using the PCLAMP computer program. Bipolar tungsten electrodes were placed at the stratum radiatum to stimulate the Schaeffer collaterals or very close to the intracellular electrode to directly stimulate the basket interneurons at the pyramidal layer. RESULTSExogenous GABA application to CAl pyramidal cell somata ( Fig. 1 A and B) elicited a hyperpolarizing response. It was often possible to discriminate two components within the GABA-elicited hyperpolarization. An initial fast-hyperpolarizing component (Fig. 2A1 Left, red trace) reversed at about -70 mV (±5) (Fig. 2 Al and C). This fast component was blocked by furosemide (0.8 mM), GABAA receptor-mediated Cl-pump blocker (7) and bicuculline methiodide (BMI), a GABAA receptor blocker (Fig. 2 A2). These observations are consistent with previous findings (6,8,9), and can be explained by GABAA receptor-mediated opening of Cl-channels (10, 11). A later, slower, and somewhat variable hyperpolarizing component (Fig. 2A1, red trace) was blocked by phaclofen ( Fig. 2 A2) but not by furosemide and can be explained by GABAB receptor-mediated opening of K+ channels (12, 13). The cell-membrane voltage changes to repetitive hyperpolarizing current pulses during the GABA responses were reduced, indicating that GABA applications caused a net increase in membrane conductance.GABA application paired with postsynaptic depolarization (Fig. 1B2) was initially followed by ...

GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations

“…In both culture and acute hippocampal, coincident pre-and postsynaptic spiking or postsynaptic firing of hippocampal neurons led to a persistent decrease in GABAergic synaptic strength, associated with a depolarizing shift of the reversal potential of GABA A receptor-mediated synaptic potentials (E GABA ). Similarly, pairing exogenously applied GABA with postsynaptic depolarization leads to a long-lasting transformation of hyperpolarizing GABAergic responses into depolarizing responses (129). GABA A receptors are permeable to chloride, and the intracellular concentration is regulated by different chloride cotransporters (499).…”

Long-Lasting GABA-Mediated Depolarization Evoked by High-Frequency Stimulation in Pyramidal Neurons of Rat Hippocampal Slice Is Attributable to a Network-Driven, Bicarbonate-Dependent K+Transient

“…11) are consistent with a delayed, [K ϩ ] o -mediated effect. Formally, the I-V characteristics of a K ϩ -evoked depolarizing current (I K ) can be derived easily from the Goldman-HodgkinKatz constant field current equation: Strongly depolarizing GABAergic postsynaptic responses are associated with certain kinds of long-term changes in synaptic efficacy (Collin et al, 1995), in the generation of epileptiform activity (Taira et al, 1997) (see also Stasheff et al, 1993), and in the immature nervous system (Cherubini et al, 1991). It will be interesting to see in future work whether, and to what extent, activity-induced [K ϩ ] o shifts are involved in the diverse phenomena that involve long-lasting GABAergic depolarizing responses in the developing and mature brain.…”

Mesenteric Vasodilation Mediated by Endothelial Anandamide Receptors

“…7,8 Neurons in the brain can synthesize anandamide 9 and 2-AG, 10 and both substances have been shown to influence central neural functions, such as long-term potentiation. 10,11 Peripheral tissues also contain anandamide [12][13][14] and 2-AG. 7,15,16 Plant-derived cannabinoids can produce cardiovascular effects, including hypotension, 17 that also can be elicited by anandamide 18 -20 and 2-AG.…”