Modulation of excitatory transmission at the rat medial vestibular nucleus synapse.
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Animals↗
Biomedical subjects
J P Gallagher
Publications and source records attributed to J P Gallagher.
Burst firing of rat septal neurons induced by 1S,3R-ACPD requires influx of extracellular calcium.
We have demonstrated that burst firing in rat dorsolateral septal nucleus neurons is a specific response following activation of metabotropic glutamate receptors. Now we report that the burst firing induced by 1S,3R-ACPD (1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid), a selective agonist, is blocked by inorganic calcium channel blockers. Our data suggest that influx of external calcium is required for this metabotropic glutamate response. Intracellular second messenger pathways coupled to the metabotropic glutamate receptor may be more complex than releasing calcium from IP3-sensitive internal stores as is currently hypothesized.
Animals↗
Direct muscarinic and nicotinic receptor-mediated excitation of rat medial vestibular nucleus neurons in vitro.
We have utilized intracellular recording techniques to investigate the cholinoceptivity of rat medial vestibular nucleus (MVN) neurons in a submerged brain slice preparation. Exogenous application of the mixed cholinergic agonists, acetylcholine (ACh) or carbachol (CCh), produced predominantly membrane depolarization, induction of action potential firing, and decreased input resistance. Application of the selective muscarinic receptor agonist muscarine (MUSC), or the selective nicotinic receptor agonists nicotine (NIC) or 1,1-dimethyl-4-phenylpiperazinium (DMPP) also produced membrane depolarizations. The MUSC-induced depolarization was accompanied by decreased conductance, while an increase in conductance appeared to underlie the NIC- and DMPP-induced depolarizations. The muscarinic and nicotinic receptor mediated depolarizations persisted in tetrodotoxin and/or low Ca2+/high Mg2+ containing media, suggesting direct postsynaptic receptor activation. The MUSC-induced depolarization could be reversibly blocked by the selective muscarinic-receptor antagonist, atropine, while the DMPP-induced depolarization could be reversibly suppressed by the selective ganglionic nicotinic-receptor antagonist, mecamylamine. Some neurons exhibited a transient membrane hyperpolarization during the depolarizing response to CCh or MUSC application. This transient inhibition could be reversibly blocked by the gamma-aminobutyric acid (GABA) antagonist, bicuculline, suggesting that the underlying hyperpolarization results indirectly from the endogenous release of GABA acting at GABA receptors. This study confirms the cholinoceptivity of MVN neurons and establishes that individual MVN cells possess muscarinic as well as nicotinic receptors. The data provide support for a prominent role of cholinergic mechanisms in the direct and indirect regulation of the excitability of MVN neurons.
Animals↗
Adenosine inhibits the synaptic potentials in rat septal nucleus neurons mediated through pre- and postsynaptic A1-adenosine receptors.
Intracellular and voltage-clamp recordings were made from neurons in rat brain slices containing dorsolateral septal nucleus (DLSN), in vitro. Bath application of adenosine (100 microM) produced a hyperpolarization (2-15 mV) in 46% of DLSN neurons (AH-neurons); in the remaining 54% neurons (non-AH-neurons), no hyperpolarization to adenosine was observed. Adenosine (1-300 microM) depressed not only the excitatory postsynaptic potential (EPSP) but also the inhibitory postsynaptic potential (IPSP) and the late hyperpolarizing potential (LHP) evoked by stimulation of the hippocampal CA3 area or the fimbria/fornix pathway in both AH- and non-AH-neurons. In non-AH-neurons, adenosine did not block current responses resulting from glutamate, muscimol or baclofen applied directly to DLSN neurons. In AH-neurons, adenosine partially depressed the baclofen-induced outward current. Adenosine did not block the directly-evoked IPSP (monosynaptic IPSP) as well as the glutamate-induced (hyperpolarizing) postsynaptic potential (PSP) that is mediated by GABA released from interneurons. These results suggest that adenosine does not directly inhibit the release of GABA. The effects of adenosine was mimicked by selective A1-receptor agonists and was blocked by selective A1-receptor antagonists. Pertussis toxin (PTX) blocked the hyperpolarization induced by adenosine or baclofen applied exogenously. Adenosine consistently produced presynaptic inhibition of the EPSP even in DLSN neurons treated with PTX. We conclude that adenosine inhibits neurotransmission between the hippocampus and septum through activation of pre- and postsynaptic A1-receptors which couple with G-proteins of different PTX-sensitivity or with distinct transduction processes at pre- vs. postsynaptic sites.
Adenosine↗
Spontaneous bursting and non-bursting activity in morphologically identified neurons of the rat dorsolateral septal nucleus, in vitro.
Membrane potential-dependent changes in the repetitive firing properties of morphologically identified rat dorsolateral septal nucleus neurons were investigated in a submerged slice preparation using intracellular recording techniques and lithium acetate-Lucifer Yellow-filled microelectrodes. The results indicate that the majority of dorsolateral septal nucleus neurons are capable of burst firing and suggest, moreover, the existence of neuronal subtypes with distinct differences in spike waveform and the pattern of spontaneous activity. In the largest proportion of neurons, single spike activity predominated at membrane potentials near rest while burst-like discharges prevailed at more hyperpolarized membrane potentials. Less frequently observed were neurons exhibiting different burst waveforms at various membrane potentials. In a few neurons, hyperpolarization slowed neuronal firing but did not elicit burst-like discharges. Characteristics such as the presence of burst or single spike discharges, spike afterpotentials, and the membrane potential dependence of repetitive firing patterns did not appear to be closely associated with membrane time constant, membrane resistance, or resting membrane potential. A detailed examination of the somatodendritic and axonal morphology of the Lucifer Yellow-filled cells revealed that these electrophysiologically identified neurons in the dorsolateral septal nucleus are morphologically heterogeneous. However, there did not appear to be any correlation between a particular somatodendritic morphology and the expression of a distinct spontaneous firing pattern. The present findings demonstrate that neurons in the rat dorsolateral septal nucleus are morphologically diverse and capable of intrinsically generating rhythmic neuronal activity. Similar patterns of rhythmic neuronal firing in vivo may provide a substrate for the integration of afferent neuronal activity and have a central role in intraseptal circuitry necessary for generation of hippocampal theta rhythm.
Acetates↗
Metabotropic glutamate receptors are required for the induction of long-term potentiation.
Recent observations have led to the suggestion that the metabotropic glutamate receptor may play a role in the induction or maintenance of long-term potentiation (LTP). However, experimental evidence supporting a role for this receptor in the induction of LTP is still inconclusive and controversial. Here we report that, in rat dorsolateral septal nucleus (DLSN) neurons, which have the highest density of metabotropic receptors and show functional responses, the induction of LTP is not blocked by the NMDA receptor antagonist 2-amino-5-phosphonovalerate, but is blocked by two putative metabotropic glutamate receptor antagonists, L-2-amino-3-phosphonopropionic acid and L-2-amino-4-phosphonobutyrate. Furthermore, superfusion of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, a selective metabotropic glutamate agonist, resulted in a long-lasting potentiation of synaptic transmission similar to that induced by tetanic stimuli. Our results demonstrated that activation of postsynaptic metabotropic receptors is both necessary and sufficient for the induction of LTP in the DLSN, and we suggest that such a mechanism may be important at other CNS synapses.
2-Amino-5-phosphonovalerate↗
Metabotropic glutamate receptor agonists potentiate a slow afterdepolarization in CNS neurons.
We have previously reported that, in the rat dorsolateral septal nucleus (DLSN), metabotropic glutamate receptor (met-GluR) agonists evoked a slow depolarization accompanied by an increase in membrane conductance and burst firing. We have speculated that the burst firing elicited by met-GluR agonists may be due to activation or enhancement of a non-specific cation current, which exists in some DLSN neurons. Now we report that a slow afterdepolarization (sADP) mediated by a non-specific cation current was potentiated by both 1S,3R-ACPD and quisqualate. In addition, met-GluR agonists unmask a sADP in DLSN neurons which did not show a sADP under control conditions. Our data suggest that a non-specific cation current can be potentiated by activation of the met-GluR.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Trans-ACPD (trans-D,L-1-amino-1,3-cyclopentanedicarboxylic acid) elicited oscillation of membrane potentials in rat dorsolateral septal nucleus neurons recorded intracellularly in vitro.
Glutamate receptors coupled to phosphoinositol turnover have been identified recently and named 'metabotropic' receptors. However, the exact functional roles of these receptors are still unknown. Trans-ACPD (trans-D,L-1-amino-1,3-cyclopentanedicarboxylic acid) is suggested to be the only selective agonist for metabotropic glutamate receptors. Here we report that trans-ACPD elicits membrane potential depolarization with oscillation of dorsolateral septal nucleus neurons recorded intracellulary in vitro. Our experiments also suggested that there may be multiple interactions between ionotropic quisqualate receptors and metabotropic glutamate receptors. The burst firing induced by high concentrations of trans-ACPD suggests that excessive activation of metabotropic glutamate receptors may lead to cellular toxicity or be associated with clinical disorders such as epilepsy.
Animals↗
Somatostatin induced hyperpolarization of septal neurons is not blocked by pertussis toxin.
The coupling of postsynaptic somatostatin receptors to pertussis toxin (PTX) sensitive guanine nucleotide regulatory proteins (G proteins) was investigated in dorsolateral septal nucleus (DLSN) neurons using a submerged brain slice preparation and intracellular recording techniques. Rats were pretreated with PTX i.c.v. and neuronal responsivity to somatostatin and baclofen, a selective GABAB receptor agonist, tested using a submerged brain slice preparation and intracellular recording techniques. In tissue obtained from rats pretreated with PTX (2.5 micrograms) for 2-5 days, somatostatin applied by superfusion (0.1 microM) produced membrane hyperpolarization and decreased the membrane resistance of DLSN neurons. Hyperpolarizing effects of somatostatin persisted in the presence of tetrodotoxin (0.3 microM) blocking synaptic transmission. Current-voltage relations of the somatostatin-induced, PTX-resistant hyperpolarization indicated a reversal potential close to the equilibrium potential for potassium ions. Membrane hyperpolarizations in PTX treated tissue were similar to those recorded in tissue from vehicle control or untreated rats. Hyperpolarizing responses to the selective GABAB receptor agonist baclofen, however, were blocked by the PTX treatment used in the present study. Our findings suggest that the postsynaptic inhibitory effects of somatostatin in the DLSN is not mediated by a somatostatin receptor coupled to PTX-sensitive G proteins. These G proteins, however, appear to be an essential link in the postsynaptic GABAB receptor-mediated response of DLSN neurons.
Animals↗
Hippocampal RSA and DLSN neurons.
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Atropine↗
Motor neuron syndrome after electric shock.
Presented here are 17 individuals with motor neuron disease that followed a severe electric shock. All were under the age of 45 when their motor disorder began. Five developed the illness within 24-36 months of the electrical accident and 12 not until decades later. In 14 cases only a single, but severe, shock had been received while in three others multiple, but substantial, jolts of electricity had been sustained. All 17 were males and all but one are still alive.
Adult↗
Pharmacology of nicotinic receptor-mediated inhibition in rat dorsolateral septal neurones.
1. Intracellular electrophysiological techniques were employed to investigate the effects of nicotinic receptor stimulation on rat dorsolateral septal nucleus (DLSN) neurones in a submerged rat brain slice preparation. 2. Acetylcholine (in the presence of the muscarinic antagonist, atropine), nicotine or dimethylphenylpiperazinium (DMPP), applied either by pressure ejection or superfusion, produced predominantly a membrane potential hyperpolarization. 3. Following concentration-response comparisons, DMPP appeared to exhibit fewer desensitizing properties and greater efficacy than nicotine with half-maximal hyperpolarizing responses attainable at 3 and 10 microM, respectively. 4. Pharmacological analyses revealed that the agonist-induced membrane hyperpolarization was sensitive to antagonism by mecamylamine (50-100 microM) and neuronal bungarotoxin (0.2-0.3 microM), but not alpha-bungarotoxin (0.5-1.0 microM), curare (10-50 microM) or dihydro-beta-erythroidine (50-100 microM). 5. Hyperpolarizing responses to DMPP were found to reverse near the equilibrium potential for potassium and were sensitive to changes in extracellular potassium concentration as predicted by the Nernst equation. Under single-electrode voltage clamp, application of DMPP produced an outward current (75-100 pA) which approached reversal at around -88 mV. These findings indicated that the hyperpolarizing response to nicotinic receptor stimulation was mediated by changes in membrane permeability to potassium. 6. DMPP-induced membrane hyperpolarization resulted from a direct action on postsynaptic DLSN neurones since the response persisted under conditions of superfusion with calcium-free/high-magnesium media or tetrodotoxin; both conditions blocked orthodromically induced neurotransmission. The hyperpolarizing response remained unaltered in TTX but was diminished in calcium-free/high-magnesium media. Further studies revealed blockade of the DMPP response following intracellular injection of EGTA. This response was also sensitive to antagonism by various calcium-dependent potassium channel blockers including apamin, barium and tetraethylammonium. 7. Our studies reveal a novel class of CNS nicotinic receptor whose action upon stimulation by an agonist results in a membrane hyperpolarization via a calcium-dependent increase in potassium ion conductance.
Acetylcholine↗
Before starting resuscitation first know what you are getting into.
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Adult↗
Somatostatin depresses GABA receptor-mediated inhibition in the rat dorsolateral septal nucleus.
The effect of somatostatin-14 (SS-14) on gamma-aminobutyric acid (GABA)-mediated inhibitory neurotransmission in the dorsolateral septal nucleus (DLSN) was investigated using a submerged slice preparation and intracellular recording techniques. Somatostatin-14 applied by superfusion or by pressure ejection from micropipettes predominantly inhibited the intracellularly recorded fast inhibitory postsynaptic potential (fIPSP) and late hyperpolarizing potential (LHP) elicited by focal electrical stimulation of the DLSN. The decreases in LHP and fIPSP amplitude occurred at low concentrations of peptide, in the absence of appreciable changes in the passive-membrane properties of postsynaptic neurons, and outlasted the membrane hyperpolarizing effect produced by SS-14 at higher concentrations. The ability of SS-14 to modulate postsynaptic GABA receptor responses underlying the fIPSP and LHP were investigated by applying baclofen, a selective GABAB receptor agonist, and isoguvacine, a selective GABAA receptor agonist, by pressure ejection. Hyperpolarizing responses to GABAA and GABAB receptor stimulation were significantly decreased during superfusion of SS-14. Tetrodotoxin applied by superfusion blocked electrically evoked synaptic potentials but not the depressant effect of SS-14 on baclofen- or isoguvacine-induced hyperpolarization. Facilitation of the fIPSP or LHP by SS-14 also occurred but less frequently and consistently than the depressant action. Excitatory postsynaptic potentials and membrane response to NMDA or quisqualate appeared unaltered by bath-applied SS-14. These findings suggest a novel postsynaptic action of SS-14 leading to depression of synaptic responses mediated by GABAA and GABAB receptors. Synaptically released SS-14 in the DLSN may participate in modulation of feedforward and/or feedback inhibitory mechanisms coordinating DLSN function in the septo-hippocampal system.
Animals↗
Facilitatory action of muscarine on the slow afterdepolarization of rat dorsolateral septal nucleus neurons in vitro.
Intracellular recordings were made from an isolated rat brain slice preparation containing the dorsolateral septal nucleus (DLSN). Calcium-dependent slow afterdepolarizations (slow-ADPs) were observed in a population of neurons, which exhibited bursts of action potentials. Bath application of muscarine (10-20 microM) augmented the slow-ADP and triggered burst firing on top of the slow-ADP. This effect of muscarine was blocked by atropine (1 microM). Muscarine augmented the slowly decaying inward current (slow-ADC) recorded by voltage clamping the afterpotential of cathodally-evoked spikes. Our data suggest that some of the burst-like activity induced by muscarine in a select population of rat DLSN neurons is mediated partly by augmentation of the current which underlies the slow-ADP.
Animals↗
Histamine depolarizes rat medial vestibular nucleus neurons recorded intracellularly in vitro.
The effects of histamine (HA) on the resting membrane potential and input resistance of rat medial vestibular nucleus (MVN) neurons were investigated using intracellular recording techniques from a submerged brain slice preparation. The exogenous application of HA predominantly produced a concentration-dependent membrane depolarization and induction of action potential firing. The depolarization exhibited a rapid onset, a slow recovery, and usually occurred in the absence of any apparent change in conductance. These effects of HA could be mimicked by the H2-agonist impromidine and were reversibly blocked by the H2-antagonist cimetidine. Tetrodotoxin (TTX) or low calcium/high magnesium-containing media failed to block completely the HA-induced depolarization supporting a direct postsynaptic receptor mediated action of HA. The diminished HA-induced depolarization observed following pretreatment with TTX cannot exclude an additional presynaptic action by HA. The present findings reveal that HA exerts a novel direct excitation of rat MVN neurons through an H2-receptor.
Action Potentials↗
A calcium-dependent slow afterdepolarization recorded in rat dorsolateral septal nucleus neurons in vitro.
1. Conventional intracellular and single-electrode voltage-clamp recordings were obtained from rat brain slices containing dorsolateral septal nucleus (DLSN) neurons in vitro. 2. We observed a slow afterdepolarizing potential (slow-ADP) that lasted up to several seconds (half-decay time was in the range of 0.7-1.4 s) in almost 15% of DLSN neurons; these same neurons could exhibit burst firing activity. The amplitude of this slow-ADP was not affected by hyperpolarization of the membrane potential. 3. The slow-ADP was associated with an increased membrane conductance. Hybrid voltage clamping of the slow-ADP revealed a transient slow inward current (slow-ADC). The current-voltage relationship of the slow-ADC was linear between -40 and -100 mV and generated an extrapolated reversal potential of -30 mV. 4. We investigated the ionic mechanism of the slow-ADP in the rat DLSN. Slow-ADPs were not blocked by 1 microM tetrodotoxin (TTX) but were markedly depressed by 200 microM Cd2+, Ca2(+)-free, low-Na+ solutions, and the intracellular injection of ethylene glycol-bis(B-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). Neither diltiazam (10 microM), an L-type Ca2+ channel blocker nor omega-conatoxin (0.2-2.5 microM), an N-type Ca2+ channel blocker affected the slow-ADP. Similarly, the slow-ADP was not affected in a low-Cl- solution. On the other hand, the slow-ADP was enhanced in a K(+)-free solution. In addition, the slow-ADP was not affected by 1 mM kynurenic acid, a broad-spectrum excitatory amino acid antagonist. 5. We conclude that the slow-ADP in the rat DLSN is mediated by a novel Ca2(+)-dependent, Na(+)-dependent, and nonsynaptic inward current that may be similar to the Ca2(+)-activated nonspecific cation channel currents (i.e., CAN-currents) described in various tissues. This current appears to underlie some forms of spontaneous bursting activity recorded from rat DLSN neurons. It may also be responsible for some types of bursting activity recorded in other CNS neurons.
Action Potentials↗
Adenosine inhibits a GABAB receptor-mediated hyperpolarizing postsynaptic potential in neurons of rat septal nuclei.
Intracellular recordings were made from neurons of rat dorsolateral septal nucleus (DLSN), in vitro. Adenosine and 2-chloroadenosine (1-500 microM) hyperpolarized DLSN neurons and blocked the excitatory postsynaptic potential (EPSP) and the late hyperpolarizing potential (LHP) in the presence of bicuculline. Adenosine did not depress the glutamate-induced potential. Bath-application of adenosine depressed the baclofen-induced potential in 60% of the neurons. Adenosine also inhibited the LHP in the remaining 40% of neurons, while it did not depress the baclofen-induced potential in these neurons. These results indicate that adenosine inhibits the EPSP pre-synaptically whereas it inhibits the LHP both pre- and postsynaptically in rat septal nuclei.
Adenosine↗