Glutamic acid decarboxylase (GAD) immunocytochemistry of developing rabbit hippocampus

Dd, Kunkel; Ae, Hendrickson; Jy, Wu; Schwartzkroin, PA

doi:10.1523/jneurosci.06-02-00541.1986

Cited by 58 publications

(40 citation statements)

References 24 publications

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“…A direct test of this hypothesis would be to examine the sensitivity of the L-M interneuron-evoked IPSPs in pyramidal cells to GABA, receptor antagonist. It should be noted that intemeurons similarly located in stratum lacunosum-moleculare are immunoreactive for glutamic acid decarboxylase (GAD; the synthesizing enzyme for GABA; Somogyi et al, 1984;Kunkel et al, 1986) and for GABA (Gamrani et al, 1986) and, thus, may use GABA as neurotransmitter. The L-M interneurons we have recorded from have similar cellular morphology (Lacaille and Schwartzkroin, 1988) and may be part of this GABAergic cell population.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it appears that both basket cells and O/A intemeurons mediate feedforward and feedback inhibition of CA1 pyramidal cells. Since intemeurons similar to basket cells and O/A intemeurons (although not physiologically identified specifically as such) are immunoreactive for GABA (Gamrani et al, 1986) and GAD (Ribak et al, 1978;Kunkel et al, 1986), this feedforward and feedback inhibition is likely to be GABA mediated (Alger and Nicoll, 1982a, b).…”

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confidence: 99%

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

1988

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Simultaneous intracellular recordings were obtained from stratum lacunosum-moleculare (L-M) interneurons and CA1 cells, and their local circuit synaptic interactions were examined. Synaptic interactions with pyramidal cells were evaluated in both intrasomatic and intradendritic pyramidal cell recordings. Stimulation of L-M interneurons evoked small- amplitude IPSPs in 21% of intrasomatic (9/42 cell pairs) and in 26% of intradendritic (11/43) pyramidal cell recordings. The IPSP mean peak amplitude was 0.91 mV for intrasomatic and 0.67 mV for intradendritic recordings. IPSPs had slow onset and decay (approximately 80–90 msec), decreased in amplitude with membrane hyperpolarization, and were not associated with any apparent change in input resistance. No physiologic evidence of synaptic connections was found from pyramidal cells to L-M interneurons. Inhibitory synaptic interactions were also seen between L- M interneurons and stratum pyramidale interneurons (2 of 4 cell pairs). The IPSPs recorded in pyramidale interneurons were similar to the IPSPs recorded in pyramidal cells. During simultaneous recordings, L-M interneurons were activated at a shorter latency, i.e., in a feedforward manner with respect to pyramidal cells. Thus, L-M interneurons may mediate feedforward inhibition of CA1 pyramidal cells. The L-M interneuron-evoked IPSPs in pyramidal cells share some characteristics of the late IPSP recorded in CA1 pyramidal cells and may therefore contribute to this component of the IPSP.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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

1988

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“…The animals were anesthetized and perfused with 3% paraformaldehyde in 0.1 M phosphate buffer (pH 7.4) containing 0.34% I-lysine and 0.05% sodium m-periodate (Kunkel et al, 1986). Brains were postfixed for 2-24 hr in the same fixative at 4°C and the hippocampus removed.…”

Section: Methodsmentioning

confidence: 99%

Inhibition in kainate-lesioned hyperexcitable hippocampi: physiologic, autoradiographic, and immunocytochemical observations

et al. 1988

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Following kainate lesions of hippocampal subfield CA3, the remaining CA 1 pyramidal cells become hyperexcitable. This lesion is of interest because, morphologically, it resembles the damage often seen in cases of temporal lobe epilepsy; it may provide insight into the consequences of such cell loss in humans. The hyperexcitability in CA 1 is associated with a loss of both early and late IPSPs. At long postlesion latencies (2–4 months) inhibition shows partial recovery and the hyperexcitability subsides. The intent of the present work was to determine if alterations in CA 1 excitability and functional inhibition postlesion are correlated with changes in morphologic and physiologic indicators of inhibitory interneuron function or with alterations in binding sites for inhibitory transmitters. Using GAD immunocytochemistry, we found no acute or chronic lesion-induced decrease in numbers of CA 1 interneurons or in qualitative characteristics of the pericellular distribution of their terminals in CA 1 stratum pyramidale. Intracellular recordings from identified cells in CA 1 indicated that putative interneurons were viable in hyperexcitable tissue. It was further observed that “recovery” in tissue studied 2–4 months postlesion primarily involved the early IPSP; the late IPSP failed to reappear. Quantitative in vitro autoradiographic analysis of 3H-flunitrazepam--a marker for the early IPSP associated GABAA receptor complex--indicated that hyperexcitability was associated with an increase in GABAA receptor number in CA 1; receptor binding returned to normal at long postlesion latencies as the early IPSP returned and hyperexcitability subsided. Finally, hyperexcitable pyramidal cells were found to retain their responsivity to exogenously applied GABA. These data indicate that much of the cellular machinery necessary for inhibition is retained in CA 1, despite lesion-induced hyperexcitability. We suggest that the acute loss of the IPSP after kainate lesion is due to a transient disconnection between inhibitory and excitatory elements in CA 1 and/or to a loss of normal afferent drive from CA3 onto some CA 1 interneurons. We further suggest that incomplete recovery can be explained by abnormalities that occur as neuroplastic rearrangements in response to deafferentation of CA 1. The relevance of these studies to human hippocampal necrosis and to other models of focal epilepsy is discussed.

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“…In the presence of bicuculline, it is reasonable to expect that there is also an enhanced excitation of inhibitory interneurons relative to control conditions. Furthermore, inhibitory synapses have been shown to exist on GABAergic interneurons (Schwartzkroin & Mathers, 1978;Knowles et al 1984;Kunkel, Hendrickson, Wu & Schwartzkroin, 1986). Bicuculline will therefore also result in a disinhibition of interneurons and, consequently, an enhanced release of GABA.…”

Section: Generation Of Paroxysmal Inhibitory Potentialsmentioning

confidence: 99%

Paroxysmal inhibitory potentials mediated by GABAB receptors in partially disinhibited rat hippocampal slice cultures.

Scanziani

Gähwiler

Thompson

1991

The Journal of Physiology

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SUMMARY1. Intracellular recording techniques were used to study synaptic potentials in CA3 pyramidal cells elicited with mossy fibre stimulation in partially disinhibited hippocampal slice cultures. Two experimental protocols were used: (1) high concentrations (20-40 gM) of the A-type y-aminobutyric acid (GABAA) receptor antagonist bicuculline plus low concentrations (2-4 /sM) of the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), or (2) low concentrations (1-2 5 ,lM) of bicuculline alone.2. Under the first condition, stimulation of mossy fibre afferents evoked epileptic bursts alternating with a response consisting of an excitatory postsynaptic potential (EPSP) followed by an unusually large and long-lasting hyperpolarizing potential with a maximal amplitude in the range of -30 mV from the resting membrane potential.3. This paroxysmal inhibitory potential (PIP) had a reversal potential near that of potassium. The amplitude of the PIP was not dependent on action potentials superimposed on the preceding EPSP, and was present in cells recorded with microelectrodes containing the Ca2" chelator EGTA. These data suggest that the PIP is not a Ca2"-activated K+ potential.4. The PIP was prolonged by the GABA-uptake blocker nipecotic acid, was reduced by hyperpolarizing interneurons with the opioid agonist FK 33-824, and was abolished by the GABAB-receptor antagonist CGP 35 348. These data indicate that the PIP is mediated by the activation of GABAB receptors following GABA release from interneurons.5. The NMDA-receptor antagonist D-2-amino-5-phosphonovalerate (D-APV) strongly reduced the amplitude of the PIP, but had no effect on the GABAB receptor-mediated inhibitory postsynaptic potential (IPSP) under control conditions.6. Under the first condition, regular stimulation elicited a cyclical pattern of evoked responses. There was either an alternation between an epileptic burst and a PIP or, at shorter interstimulus intervals, a sequence of gradually increasing PIPs followed by an epileptic burst, which then reset the cycle. Under the second condition, in low concentrations of bicuculline alone, the early GABAA-mediated IPSP was little affected, but the late GABAB-mediated IPSP was greatly enhanced. These enhanced late IPSPs were comparable in amplitude and duration to the PIPs seen under the first conditions, could exhibit cyclical behaviour, and were reduced by D-APV.8. Application of CGP 35 348 abolished the late IPSP under control conditions, but had no effect on hippocampal excitability. In contrast, CGP 35 348 blocked the PIP elicited in low bicuculline, and consequently led to intense epileptic discharge.9. We suggest that the amplification of GABAB receptor-mediated synaptic potentials after partial disinhibition may be an important endogenous compensatory mechanism preventing epileptogenesis.

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Glutamic acid decarboxylase (GAD) immunocytochemistry of developing rabbit hippocampus

Cited by 58 publications

References 24 publications

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

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

Inhibition in kainate-lesioned hyperexcitable hippocampi: physiologic, autoradiographic, and immunocytochemical observations

Paroxysmal inhibitory potentials mediated by GABAB receptors in partially disinhibited rat hippocampal slice cultures.

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