Factors contributing to the decay of the stimulus-evoked IPSC in rat hippocampal CA1 neurons

1994 ◽  
Vol 72 (6) ◽  
pp. 2911-2926 ◽  
Author(s):  
A. Roepstorff ◽  
J. D. Lambert
Keyword(s):  
Gabaa Receptor ◽  
Transmitter Release ◽  
Gabab Receptors ◽  
Gaba Uptake ◽  
Uptake System ◽  
Paired Pulse ◽  
Synaptic Receptors ◽  
Kinetics Of ◽  
Paired Pulse Depression ◽  
Pulse Stimulation

1. Monosynaptic gamma-aminobutyric acid-A (GABAA)-mediated inhibitory postsynaptic currents (IPSCs) were evoked in CA1 pyramidal neurons in the hippocampal slice preparation by direct stimulation of the interneurons in the presence of glutamatergic blockers and intracellular QX-314 to block GABAB-mediated postsynaptic inhibition. 2. Paired-pulse stimulation was used to activate presynaptic GABAB autoreceptors and thereby reduce the amount of transmitter release. This caused paired-pulse depression, persisting for > 3 s, and maximal at interpulse intervals between 100 and 250 ms where peak current (Ipeak) was decreased by 29.7% and decay time (t1/2) was decreased by 44.7%. There was clear correlation between changes in Ipeak and t1/2 at all interpulse intervals. 3. With paired-pulse stimulation, the decay of the second IPSC in most cells (12/18) could be resolved into two components, Ifast and Islow, each decaying monoexponentially with tau fast = 14.10 ms and tau slow = 58.87 ms. The faster decay during paired-pulse depression was predominantly caused by a larger Ifast fraction, which accounted for 27.5% of Ipeak in a single control IPSC and 79.3% at an interpulse interval of 250 ms. 4. Reducing the probability for transmitter release at all active sites by reducing [Ca2+]o from 2 mM to 1 mM decreased Ipeak by 49.7%, reduced paired-pulse depression, and partly mimicked the changes in decay kinetics seen after activation of presynaptic GABAB receptors. Lowering the stimulating intensity to 10% of the maximal value decreased Ipeak by 73.8%, but hardly affected the decay of the IPSC and the paired-pulse depression. 5. Application of the selective blocker of GABA uptake, tiagabine (20-50 microM), increased t1/2 of a single IPSC by 114% without affecting Ipeak. The increase was caused solely by an increase in tau slow of 141%. On the other hand, the benzodiazepine agonist midazolam (2 microM), selectively increased tau fast. It therefore is suggested that tau fast reflects the kinetics of the GABAA receptor/ionophore complex and tau slow the efficiency of the GABA uptake system. 6. The findings show that GABA activates postsynaptic receptors throughout the tail of a single IPSC. This could be caused by reactivation of synaptic receptors or activation of extrasynaptic receptors. The decay therefore is limited mainly by the efficiency of the uptake system. An IPSC that is maximally depressed by paired-pulse stimulation is mediated primarily by a single activation of synaptic receptors, and the decay is limited mainly by the kinetics of the GABAA receptor/ionophore complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Discrimination of post- and presynaptic GABAB receptor-mediated responses by tetrahydroaminoacridine in area CA3 of the rat hippocampus

1993 ◽  
Vol 69 (2) ◽  
pp. 630-635 ◽  
Author(s):  
N. A. Lambert ◽  
W. A. Wilson
Keyword(s):  
Gabaa Receptor ◽  
Gabab Receptor ◽  
Hippocampal Slices ◽  
Outward Current ◽  
Gabab Receptors ◽  
Rat Hippocampus ◽  
Stratum Radiatum ◽  
Paired Pulse ◽  
Paired Pulse Depression ◽  
Area Ca3

1. The effects of the K+ channel blocker 9-amino-1,2,3,4-tetrahydroacridine (THA) on the actions of baclofen and gamma-aminobutyric acid (GABA) at post- and presynaptic GABAB receptors were studied with whole-cell voltage-clamp recording in area CA3 of rat hippocampal slices. 2. The effect of THA on postsynaptic GABAB receptor-mediated responses was studied in neurons perfused internally with potassium gluconate and guanosine triphosphate (GTP). At a holding potential of -70 mV, the GABAB receptor agonist (+/-)-baclofen (30 microM) induced an outward current and increased membrane conductance. In the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and (+/-)-2-amino-5-phosphonovalerate (APV), stimulation in stratum pyramidale or proximal stratum radiatum evoked GABAA receptor-mediated, fast monosynaptic inhibitory postsynaptic currents (IPSCs) and GABAB receptor-mediated, late monosynaptic IPSCs. THA (0.3 mM) blocked the baclofen-induced current and conductance increase and GABAB receptor-mediated IPSCs. 3. The effect of THA on presynaptic GABAB receptor-mediated responses was studied in neurons perfused internally with Cs+ and lidocaine N-ethyl bromide (QX-314), which blocked post-synaptic GABAB receptor-mediated responses. Stimulation in the presence of DNQX and APV evoked GABAA receptor-mediated IPSCs; when pairs of stimuli were delivered 200 ms apart the second IPSC was depressed. Baclofen reversibly depressed IPSCs, and partially occluded paired-pulse depression of IPSCs. The GABAB receptor antagonist CGP 35348 (0.5-1.0 mM) reversed baclofen-induced depression of IPSCs and partially blocked paired-pulse depression. Baclofen-induced and paired-pulse depression of IPSCs were not by affected by THA (0.3 mM). 4. Baclofen reversibly decreased the amplitude and frequency of spontaneous monosynaptic IPSCs (sIPSCs). Depression of sIPSCs by baclofen was unchanged by THA. 5. These results indicate that THA blocks the actions of baclofen and GABA at post- but not presynaptic GABAB receptors. We conclude that post- and presynaptic GABAB receptors in area CA3 of the rat hippocampus couple to different effector mechanisms; postsynaptic GABAB receptors activate THA-sensitive K+ channels, and presynaptic GABAB receptors decrease neurotransmitter release through a THA-insensitive mechanism.

Hippocampal CA1 lacunosum-moleculare interneurons: modulation of monosynaptic GABAergic IPSCs by presynaptic GABAB receptors

1995 ◽  
Vol 74 (5) ◽  
pp. 2126-2137 ◽  
Author(s):  
R. Khazipov ◽  
P. Congar ◽  
Y. Ben-Ari
Keyword(s):  
Receptor Antagonist ◽  
Transmitter Release ◽  
Gabab Receptor ◽  
Molecular Layer ◽  
Pyramidal Cells ◽  
Gabab Receptors ◽  
Stratum Radiatum ◽  
Paired Pulse ◽  
High Level ◽  
Paired Pulse Depression

1. Whole cell patch-clamp recordings were employed to characterize monosynaptic inhibitory postsynaptic currents (IPSCs) in morphologically and electrophysiologically identified interneurons located in the stratum lacunosum moleculare, or near the border of the stratum radiatum (LM interneurons), in the CA1 region of hippocampal slices taken from 3- to 4-wk-old rats. Monosynaptic IPSCs, evoked in the presence of glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM) and D-2-amino-5-phosphopentanoate (APV; 50 microM) were biphasic. The gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline (20 microM), blocked the fast IPSC, and the slow IPSC was blocked by the GABAB receptor antagonist CGP35348 (500 microM). 2. Monosynaptic IPSCs were evoked by electrical stimulation in several distant regions including the stratum radiatum, the stratum oriens, the stratum lacunosum-moleculare, and the molecular layer of dentate gyrus, suggesting an extensive network of inhibitory interneurons in the hippocampus. In paired recordings of CA1 interneurons and pyramidal cells, IPSCs were evoked by electrical stimulation of most of these distal regions with the exception of the molecular layer of dentate gyrus, which evoked an IPSC only in LM interneurons. 3. Frequent (> 0.1 Hz) stimulation depressed the evoked IPSCs. With a paired-pulse protocol, the second IPSC was depressed and the maximal depression (40-50%) was observed with an interstimulus interval of 100-200 ms. 4. The GABAB receptor agonist baclofen (1 microM) reduced the amplitude of evoked IPSCs and the paired-pulse depression of the second IPSC. The GABAB receptor antagonist CGP35348 (0.5-1 mM) had no significant effect on the amplitude of isolated IPSCs. However, CGP35348 reduced but did not fully block paired-pulse depression, suggesting that this depression is partly due to the activation of presynaptic GABAB receptors. 5. The paired-pulse depression depended on the level of transmitter release. Potentiation of synaptic release of GABA, by increasing the extracellular Ca2+ concentration to 4 mM and reducing the extracellular Mg2+ concentration to 0.1 mM, enhanced the depression. Reduction of transmitter release by increasing extracellular Mg2+ concentration to 7 mM diminished the paired-pulse depression of IPSCs. After potentiation of transmitter release, CGP35348 was less efficient in reducing the paired-pulse depression, suggesting that enhancement of depression by high-calcium/low-magnesium medium was preferentially due to the potentiation of a GABAB-independent component. 6. In summary, monosynaptic IPSCs recorded in LM interneurons show similar features to those recorded in pyramidal cells. The strong correlation between the level of transmitter release and the degree of paired-pulse depression may have important physiological consequences, because in synapses with a high level of activity and a high level of GABA release, inhibition is powerful, but depression can develop more readily.

Activation of Presynaptic GABAB Receptors Inhibits Evoked IPSCs in Rat Magnocellular Neurons In Vitro

1998 ◽  
Vol 79 (3) ◽  
pp. 1508-1517 ◽  
Author(s):  
Didier Mouginot ◽  
Samuel B. Kombian ◽  
Quentin J. Pittman
Keyword(s):  
Reversal Potential ◽  
Input Resistance ◽  
Gabab Receptors ◽  
Gaba Uptake ◽  
Kinetic Properties ◽  
Dependent Manner ◽  
Magnocellular Neurons ◽  
Paired Pulse ◽  
Endogenous Gaba

Mouginot, Didier, Samuel B. Kombian, and Quentin J. Pittman. Activation of presynaptic GABAB receptors inhibits evoked IPSCs in rat magnocellular neurons in vitro. J. Neurophysiol. 79: 1508–1517, 1998. Whole cell recordings (nystatin-perforated patch) were carried out on magnocellular neurons of the rat supraoptic nucleus (SON) to study the modulation of inhibitory postsynaptic currents (IPSCs) by γ-aminobutyric acid-B (GABAB) receptors. Field stimulation adjacent to the SON in the presence of kynurenic acid, evoked monosynaptic GABAergic IPSCs. Baclofen reversibly reduced the amplitude of the IPSCs in a dose-dependent manner (EC50: 0.68 μM) without apparent effect on the holding current ( V h = −80 mV) or input resistance and altered neither the kinetic properties, nor the reversal potential of IPSCs. Concomittant to IPSC depression, baclofen enhanced the paired-pulse ratio for two consecutive IPSCs [interstimulus interval (ISI): 50 ms], an effect consistent with a presynaptic locus of action. Both actions of baclofen were abolished by CGP35348 (500 μM), a GABAB receptor antagonist. In testing for involvement of synaptically activated presynaptic GABAB receptors, we only recorded paired-pulse facilitation at most ISIs tested (50–500 ms), suggesting that the classical GABAB autoreceptors may not normally be activated in our conditions. However, enhancement of local GABA concentration by perfusion of a GABA uptake inhibitor (NO-711) revealed an action of endogenous GABA at these presynaptic GABAB receptors. The nonselective K+ channel blocker Ba2+ abolished baclofen's effect and pertussis toxin (PTX) pretreatment (200–500 ng/ml for 18–24 h) was ineffective in blocking the baclofen-induced inhibition, making an involvement of PTX-sensitive G protein unlikely. The present results show that presynaptic GABAB receptors that are coupled to PTX-insensitive G-proteins may be activated by endogenous GABA under conditions of reduced GABA uptake, thus regulating the inhibitory synaptic input to SON.

A Novel Gaba Receptor in the Heart of a Primitive Arthropod, Limulus Polyphemus

1989 ◽  
Vol 147 (1) ◽  
pp. 421-438
Author(s):  
JACK A. BENSON
Keyword(s):  
Gabaa Receptor ◽  
Gaba Receptors ◽  
Gaba Receptor ◽  
Beat Frequency ◽  
Heart Beat ◽  
Limulus Polyphemus ◽  
Gabab Receptors ◽  
Gaba Uptake ◽  
Muscle Fibres ◽  
Sodium Pentobarbital

1. The isolated, intact heart of the marine arachnid Limulus polyphemus continues to beat in vitro for many hours. Application of γaminobutyric acid (GABA) decreased the heart beat frequency with a threshold of 3xlO−7 moll−1 and an EC50 of 2.0±0.6xlO−5 moll−1 (mean±s.D., N = 8). At lO−4moll−1 and above the heart beat was completely and reversibly inhibited. 2. The agonist potency profile of the Limulus heart chronotropic GABA receptor was very similar to that of the vertebrate GABAA receptor: muscimol > ZAPA>GABA=⋍TACA>isoguvacine>THIP>3-aminopropane sulphonic acid> imidazole-4-acetic acid ⋍ß-guanidino proprionic acid ⋍5-aminovalerate. In contrast, the antagonist profile differed dramatically: bicuculline, pitrazepin and SR 95103, as well as the channel blocker picrotoxin, were without effect at concentrations up to 10−4moll−1. 3. The benzodiazepines clorazepate, flunitrazepam, flurazepam and diazepam, as well as the barbiturate sodium pentobarbital, were without effect on the GABA response, suggesting that the Limulus heart GABA receptor is not complexed with the benzodiazepine and barbiturate modulatory subunits that characterize vertebrate GABAA receptor. 4. The GABAB ligands baclofen, phaclophen and kojic amine were inactive on the heart. However, 3-aminopropyl-phosphonous acid (CGA147 823), a potent and highly selective GABAb agonist, was the most active of the compounds tested. It inhibited the heart beat with a threshold of about SnmolP1, an EC50 of 4.0±2.7×10−7 mol1−1, and produced total inhibition of the heart at 10−5moll−1. CGA 147 823 was inactive on the locust thoracic somal GABA receptors. 5. cis-4-aminocrotonic acid (CACA), the ligand defining a proposed GAB Actype receptor, was inactive on the heart. 6. The GABA-induced inhibition of the heart beat was enhanced by pretreatment with the GABA uptake inhibitor nipecotic acid but not with sodium valproate or ß-alanine. 7. The Limulus heart chronotropic GABA receptor appears to be of a hitherto undescribed type that differs in pharmacology from the vertebrate GABAA and GABAB receptors as well as from the well-defined GABA receptors on the somata of locust neurones and the muscle fibres of insects and the nematode Ascaris.

Decreased monosynaptic GABAB-mediated inhibitory postsynaptic potentials in hippocampal CA1 pyramidal cells in the aged rat: pharmacological characterization and possible mechanisms

1995 ◽  
Vol 74 (2) ◽  
pp. 539-546 ◽  
Author(s):  
J. M. Billard ◽  
Y. Lamour ◽  
P. Dutar
Keyword(s):  
Pyramidal Cells ◽  
Gaba Release ◽  
Gabab Receptors ◽  
Aged Rats ◽  
Aged Rat ◽  
Paired Pulse ◽  
Postsynaptic Potentials ◽  
Inhibitory Postsynaptic Potentials ◽  
Bath Application ◽  
Paired Pulse Depression

1. gamma-Aminobutyric acid (GABA)-mediated inhibitory postsynaptic potentials (IPSPs) were compared in young and aged rats in CA1 area of the rat hippocampus, with the use of the in vitro intracellular recording technique. D-2-Amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were used to suppress synaptic potentials mediated by the excitatory amino acids. 2. Under these conditions, stimulation of the stratum radiatum elicited a monosynaptic fast GABAA (fIPSP) and a slow GABAB (sIPSP)-mediated IPSP. The fIPSP and the sIPSP were further isolated in the presence of the GABAB antagonist CGP 35348 or the GABAA antagonists bicuculline or picrotoxin. No age-related changes were observed in the amplitude and the duration of the fIPSP. In contrast, the amplitude (but not the duration) of the sIPSP was significantly reduced in the aged rat. 3. The postsynaptic hyperpolarization and increase in membrane conductance induced in pyramidal cells by bath application of the GABAB agonist baclofen were comparable in both groups of animals, indicating that the postsynaptic GABAB receptors are not altered in the aged rats. 4. Paired-pulse depression of IPSPs was used in young and aged rats to study possible alterations in GABA release or in presynaptic GABAB receptors that control GABA release. When fIPSPs were isolated by bath application of tetrahydro-9-aminoacridine (THA), no significant difference in the magnitude of the paired-pulse depression was observed between young and aged rats. A similar result was found with the paired-pulse depression of isolated sIPSPs in the presence of bicuculline or picrotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity-Dependent Depression of GABAergic IPSCs in Cultured Hippocampal Neurons

1999 ◽  
Vol 82 (1) ◽  
pp. 42-49 ◽  
Author(s):  
Kimmo Jensen ◽  
John D. C. Lambert ◽  
Morten Skovgaard Jensen
Keyword(s):  
Hippocampal Neurons ◽  
Time Course ◽  
Presynaptic Neuron ◽  
Paired Pulse ◽  
Whole Cell Patch Clamp ◽  
Activity Dependent ◽  
Paired Pulse Depression ◽  
Tetanic Depression ◽  
Pulse Stimulation ◽  
Cultured Hippocampal Neurons

Short-term depression of monosynaptic GABAergic inhibitory postsynaptic currents (IPSCs) evoked between pairs of cultured rat hippocampal neurons was investigated using dual whole cell patch-clamp recordings. Paired stimuli applied to the GABAergic neuron resulted in paired-pulse depression (PPD) of the second IPSC (IPSC2) at interpulse intervals from 25 to 2,000 ms. CGP 55845A, but not CGP 35348, reduced PPD marginally. Brief paired-pulse applications of exogenous GABA indicated that postsynaptic factors made only minimal contribution to PPD of IPSCs. IPSC1 and PPD was reduced on lowering [Ca2+]o and enhanced on increasing [Ca2+]o. The potassium-channel blocker 4-aminopyridine (4-AP), which increases presynaptic Ca2+ influx, enhanced IPSC1 and PPD. Chelation of residual Ca2+ in the GABAergic boutons with EGTA-AM enhanced PPD. Stimulation of the presynaptic neuron at frequencies ( f) ranging from 2.5 to 80 Hz resulted in tetanic depression of IPSCs, which declined rapidly and reached a plateau depending on f and [Ca2+]o. CGP 55845A decreased tetanic depression in the first part of the train, but this could be overcome with continued stimulation. We show that GABAergic IPSCs are robustly depressed by paired-pulse stimulation in cultured hippocampal neurons. The depression of IPSCs is mainly independent of presynaptic GABAB receptors and could be caused by depletion of releasable vesicles. Depleted synapses recover with a slow time course, depending on factors that regulate [Ca2+]i in the GABAergic boutons.

scholarly journals Axonal Modulation of Striatal Dopamine Release by Local γ-Aminobutyric Acid (GABA) Signalling

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 709
Author(s):  
Bradley M. Roberts ◽  
Emanuel F. Lopes ◽  
Stephanie J. Cragg
Keyword(s):  
Gabab Receptors ◽  
Striatal Dopamine ◽  
Aminobutyric Acid ◽  
Gaba Uptake ◽  
Short Term Plasticity ◽  
Psychomotor Disorders ◽  
Gabaa And Gabab Receptors ◽  
Uptake Transporters ◽  
Gabaergic Modulation ◽  
Da Release

Striatal dopamine (DA) release is critical for motivated actions and reinforcement learning, and is locally influenced at the level of DA axons by other striatal neurotransmitters. Here, we review a wealth of historical and more recently refined evidence indicating that DA output is inhibited by striatal γ-aminobutyric acid (GABA) acting via GABAA and GABAB receptors. We review evidence supporting the localisation of GABAA and GABAB receptors to DA axons, as well as the identity of the striatal sources of GABA that likely contribute to GABAergic modulation of DA release. We discuss emerging data outlining the mechanisms through which GABAA and GABAB receptors inhibit the amplitude as well as modulate the short-term plasticity of DA release. Furthermore, we highlight recent data showing that DA release is governed by plasma membrane GABA uptake transporters on striatal astrocytes, which determine ambient striatal GABA tone and, by extension, the tonic inhibition of DA release. Finally, we discuss how the regulation of striatal GABA-DA interactions represents an axis for dysfunction in psychomotor disorders associated with dysregulated DA signalling, including Parkinson’s disease, and could be a novel therapeutic target for drugs to modify striatal DA output.

The spinal GABA system modulates burst frequency and intersegmental coordination in the lamprey: differential effects of GABAA and GABAB receptors

1993 ◽  
Vol 69 (3) ◽  
pp. 647-657 ◽  
Author(s):  
J. Tegner ◽  
T. Matsushima ◽  
A. el Manira ◽  
S. Grillner
Keyword(s):  
Spinal Cord ◽  
Locomotor Activity ◽  
Gabaa Receptor ◽  
Gabab Receptor ◽  
Gaba Uptake ◽  
Phase Lag ◽  
Fictive Locomotion ◽  
Burst Frequency ◽  
Intersegmental Coordination ◽  
Burst Pattern

1. The effect of spinal GABAergic neurons on the segmental neuronal network generating locomotion has been analyzed in the lamprey spinal cord in vitro. It is shown that gamma-aminobutyric acid (GABA)A- and GABAB-mediated effects influence the burst frequency and the intersegmental coordination and that the GABA system is active during normal locomotor activity. 2. Fictive locomotor activity was induced by superfusing the spinal cord with a Ringer solution containing N-methyl-D-aspartate (NMDA, 150 microM). The efferent locomotor activity was recorded by suction electrodes from the ventral roots or intracellularly from interneurons or motoneurons. If a GABA uptake blocker was added to the perfusate, the burst rate decreased. This effect was counteracted by GABAB receptor blockade by phaclofen or 2-(OH)-saclofen. If instead a GABAB receptor agonist (baclofen) was added during fictive locomotion, a depression of the burst rate occurred. It was concluded that a GABAB receptor activation due to an endogenous release of GABA caused a depression of the burst activity with a maintained well-coordinated locomotor activity. 3. If a GABAA receptor antagonist (bicuculline) is applied during fictive locomotion elicited by NMDA, a certain increase of the burst rate occurred. Conversely, if a selective GABAA agonist (muscimol) was administered, the burst rate decreased. Similarly, if the GABAA receptor activity was potentiated by activation of a benzodiazepine site by diazepam, the burst rate was reduced. If, however the GABAergic effect was first enhanced by an uptake blocker (nipecotic acid), an administration of a GABAA antagonist (bicuculline) increased the burst rate, but in addition, the burst pattern became less regular with recurrent shorter periods without clear reciprocal burst activity. The GABAA receptor activity appears important for the rate control and for permitting a regular burst pattern. 4. The intersegmental coordination in the lamprey is characterized by a rostrocaudal constant phase lag of approximately 1% of the cycle duration between the activation of consecutive segments during forward swimming. This rostrocaudal phase lag can be reversed during backward swimming, which can be induced also experimentally in the isolated spinal cord by providing a higher excitability to the caudal segments. In a split-bath configuration, a GABA uptake blocker or a GABAB agonist was administered to the rostral part of the spinal cord, which caused a reversal of the phase lag as during backward swimming. If GABAA receptors were blocked under similar conditions, the intersegmental coordination became irregular. It is concluded that an increased GABA activity in a spinal cord region can modify the intersegmental coordination.(ABSTRACT TRUNCATED AT 400 WORDS)

Depolarizing actions of GABA and glycine on amphibian retinal horizontal cells

1991 ◽  
Vol 65 (3) ◽  
pp. 680-692 ◽  
Author(s):  
R. A. Stockton ◽  
M. M. Slaughter
Keyword(s):  
Gabaa Receptor ◽  
Gaba Receptors ◽  
Ganglion Cells ◽  
Light Response ◽  
Feedback System ◽  
Horizontal Cells ◽  
Gaba Uptake ◽  
Gamma Aminobutyric Acid ◽  
Ion Substitution ◽  
Chemical Coupling

1. The effects of inhibitory amino acid transmitters on horizontal cells in the superfused amphibian retina were studied by the use of conventional intracellular recording techniques. 2. Gamma-aminobutyric acid (GABA) caused a calcium-independent depolarization of horizontal cells in mud puppy and tiger salamander. This action was mimicked by muscimol but not baclofen (BAC) and blocked by bicuculline and picrotoxin (PTX), matching the GABAa receptor profile. 3. The purported GABA uptake inhibitors nipecotate (NPA) and guvacine (GUV) acted as GABAa agonists, having pharmacological properties very similar to GABA itself. These agents also activated receptors of amacrine and ganglion cells, causing membrane polarizations similar to GABA. Concentrations of these analogues that did not activate the GABAa receptor (submillimolar) did not lower the effective dose of GABA, even after prolonged application. 4. Glycine (GLY) also depolarized horizontal cells, but only in approximately 25% of the horizontal cells was the amplitude of the depolarization as great as GABA. The glycine response was blocked by both strychnine (STR, 10 microM) and PTX (100 microM). In contrast, the action of GABA was unaffected by STR. 5. Ion substitution and channel-blocking agents indicated that the effects of applied GABA and GLY were independent of both external sodium and calcium. 6. The results suggest that GABA receptors on horizontal cells may act 1) as a positive feedback system to modulate the light response and 2) as a mechanism for chemical coupling between horizontal cells.

Properties of Unitary IPSCs in Hippocampal Pyramidal Cells Originating From Different Types of Interneurons in Young Rats

1997 ◽  
Vol 77 (4) ◽  
pp. 1939-1949 ◽  
Author(s):  
Mohamed Ouardouz ◽  
Jean-Claude Lacaille
Keyword(s):  
Reversal Potential ◽  
Pyramidal Cells ◽  
Mean Amplitude ◽  
Paired Pulse ◽  
Young Rats ◽  
Different Types ◽  
The Mean ◽  
Paired Pulse Depression ◽  
Types Of Interneurons ◽  
Stimulation Of

Ouardouz, Mohamed and Jean-Claude Lacaille. Properties of unitary IPSCs in hippocampal pyramidal cells originating from different types of interneurons in young rats. J. Neurophysiol. 77: 1939–1949, 1997. Whole cell recordings were used in hippocampal slices of young rats to examine unitary inhibitory postsynaptic currents (uIPSCs) evoked in CA1 pyramidal cells at room temperature. Loose cell-attached stimulation was applied to activate single interneurons of different subtypes located in stratum oriens (OR), near stratum pyramidale (PYR), and at the border of stratum radiatum and lacunosum-moleculare (LM). uIPSCs evoked by stimulation of PYR and OR interneurons had similar onset latency, rise time, peak amplitude, and decay. In contrast, uIPSCs elicited by activation of LM interneurons were significantly smaller in amplitude and had a slower time course. The mean reversal potential of uIPSCs was −53.1 ± 2.1 (SE) mV during recordings with intracellular solution containing potassium gluconate. With the use of recording solution containing the potassium channel blocker cesium, the reversal potential of uIPSCs was not significantly different (−58.5 ± 2.6 mV), suggesting that these synaptic currents were not mediated by potassium conductances. Bath application of the γ-aminobutyric acid-A (GABAA) receptor antagonist bicuculline (25 μM) reversibly blocked uIPSCs evoked by stimulation of all interneuron subtypes. In bicuculline, the mean peak amplitude of uIPSCs recorded with potassium gluconate was reduced to 3.5 ± 4.4% of control ( n = 7). Similarly, with cesium methanesulfonate, the mean amplitude in bicuculline was 2.9 ± 3.1% of control ( n = 13). Application of the GABAB receptor antagonist CGP 55845A (5 μM) resulted in a significant and reversible increase in the mean amplitude of uIPSCs recorded with cesium-containing intracellular solution. Thus uIPSCs from all cell types appeared under tonic presynaptic inhibition by GABAB receptors. Paired stimulation of individual interneurons at 100- to 200-ms intervals did not result in paired pulse depression of uIPSCs. For individual responses, a significant negative correlation was observed between the amplitude of the first and second uIPSCs. A significant paired pulse facilitation (154.0 ± 8.0%) was observed when the first uIPSC was smaller than the mean of all first uIPSCs. A small, but not significant, paired pulse depression (90.8 ± 4.0%) was found when the first uIPSC was larger than the mean of all first uIPSCs. Our results indicate that these different subtypes of hippocampal interneurons generate Cl−-mediated GABAA uIPSCs. uIPSCs originating from different types of interneurons may have heterogeneous properties and may be subject to tonic presynaptic inhibition via heterosynaptic GABAB receptors. These results suggest a specialization of function for inhibitory interneurons and point to complex presynaptic modulation of interneuron function.

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