Comparison of the action of baclofen with gamma‐aminobutyric acid on rat hippocampal pyramidal cells in vitro.

Abstract

SUMMARY1. Intracellular recordings from CAI pyramidal cells in the hippocampal slice preparation were used to compare the action of baclofen, a y-aminobutyric acid (GABA) analogue, with GABA.2. Ionophoretic application of GABA or baclofen into stratum (s.) pyramidale evoked hyperpolarizations associated with reductions in the input resistance of the cell. Baclofen responses were easier to elicit in the dendrites than in the cell body layer. 5. The reversal potentials for the somatic GABA and baclofen responses were -70 mV and -85 mV respectively. When the membrane was depolarized, the baclofen response was reduced. This apparent voltage sensitivity was not seen with somatic GABA responses.6. Altering the chloride gradient across the cell membrane altered the reversal potential of the somatic GABA response but not that of the baclofen response. It was extrapolated that a tenfold shift in the extracellular potassium concentration would cause a 48 mV shift in the reversal potential of the baclofen response. Barium ions reduced the baclofen response, but not the GABA response.7. Orthodromic stimulation produced a fast inhibitory post-synaptic potential (i.p.s.p.) and a slow i.p.s.p. The properties of the fast and slow i.p.s.p.s were remarkably similar to those of the somatic GABA and baclofen responses, respectively.8. Application of GABA to the pyramidal cell dendrites evoked, in addition to a depolarization, two types of hyperpolarization. One type of hyperpolarization was * Present address: Merck Sharp and Dohme

Neural plasticity without postsynaptic action potentials: less-active inputs become dominant when kitten visual cortical cells are pharmacologically inhibited.

“…Second, muscimol-binding studies (32,33) demonstrate binding in kitten visual cortex with a single binding affinity and GABA-A pharmacology. Third, although binding of GABA to pre-and postsynaptic GABA-B receptors has also been demonstrated (25)(26)(27), the effects of muscimol binding to GABA-A receptors and GABA-or baclofenbinding to GABA-B receptors clearly seem to operate through different mechanisms (25)(26)(27)36 Fig. 2 a and e, and Fig.…”

“…In all cases, however, this activity has been shown to be mediated through the GABA-B receptor, at which muscimol and other GABA agonists, such as 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridine-3-ol and 3-aminopropane sulfonic acid, are not, or are only minimally, active (26)(27)(28). In addition, muscimol binding can always be antagonized by bicuculline, a GABA antagonist active at the GABA-A binding site, whereas the effects associated with binding to the GABA-B receptor are completely or largely bicuculline-insensitive (25)(26)(27)(28). In the kitten visual cortex, GABAergic inhibition is already present (29)(30)(31), and muscimol appears to bind only to GABA-A receptors (32,33).…”

“…GABA is the principal inhibitory neurotransmitter in cerebral cortex (21,22); GABA is found in all layers (23) and powerfully inhibits all, or nearly all, neurons (24). Although the inhibitory action of GABA is generally associated with a direct postsynaptic effect (25), GABA has also been shown to have a presynaptic effect-namely, that of reducing neurotransmitter release from presynaptic nerve terminals (26)(27)(28). In all cases, however, this activity has been shown to be mediated through the GABA-B receptor, at which muscimol and other GABA agonists, such as 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridine-3-ol and 3-aminopropane sulfonic acid, are not, or are only minimally, active (26)(27)(28).…”

Stratum lacunosum-moleculare interneurons of hippocampal CA1 region. II. Intrasomatic and intradendritic recordings of local circuit synaptic interactions

“…Although negative results are difficult to interpret, especially in paired intracellular recording experiments, these results are supported by the anatomical evidence and the fact that the same experimental techniques (used by the same experimenters) have yielded positive results in the cases of basket cells and O/A intemeurons (Knowles and Schwartzkroin, 198 la;Lacaille et al, 1987). The lack of excitatory connections from pyramidal cells to L-M interneurons further suggests that L-M intemeurons, unlike basket cells and O/A (1) an early IPSP mediated by C lions and thought to involve recurrent (feedback) as well as feedforward inhibitory interneurons releasing GABA at synapses located mainly on pyramidal somata and activating GABA, receptors (Kandel et al, 196 1;Andersen et al, 1964a, b;Newberry and Nicoll, 1985); and (2) a late IPSP mediated possibly by K+ ions and involving feedforward inhibitory interneurons making synapses on pyramidal cell dendrites and releasing GABA, which acts on GABA, receptors (Alger and Nicoll, 1982a, b;Newberry and Nicoll, 1985). Many aspects of the L-M interneuron-evoked pyramidal cell IPSPs suggest that these interneurons may mediate the late IPSP of CA1 pyramidal cells.…”

GIRK1 immunoreactivity is present predominantly in dendrites, dendritic spines, and somata in the CA1 region of the hippocampus

“…A GIRK-mediated K ϩ conductance is likely to attenuate synaptic currents through membrane hyperpolarization or shunting. In support of a GIRK-mediated hyperpolarization, activation of the 5HT 1A serotonin receptor, the GABA B receptor or the A 1 adenosine receptor elicits a hyperpolarizing response that is mediated by an increased G protein-activated, Ba 2ϩ -and voltage-sensitive potassium conductance in CA1 pyramidal cells (32)(33)(34)(35)(36)(37)(38)(39). At least one of these receptors (5HT 1A ) functionally couples to GIRK1 when the two proteins are coexpressed in Xenopus oocytes (13).…”