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PubMed1996

In vitro brain slice studies of the rat's dorsal nucleus of the lateral lemniscus. III. synaptic pharmacology.

1. The synaptic pharmacology of the dorsal nucleus of the lateral lemniscus (DNLL) of the rat was investigated in a brain slice preparation of the auditory midbrain. The brain slice was cut in the coronal plane and placed in a small recording chamber where warm, oxygenated saline was continuously perfused over and underneath the tissue. Intracellular recordings were made with glass microelectrodes filled with 4 M potassium acetate. Synaptic potentials were elicited by electrical stimulation of the lateral lemniscus or commissure of Probst and pharmacological effects were tested by bath application of amino acid agonists and antagonists. 2. The cells in DNLL were challenged with the excitatory amino acid (EAA) agonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), N-methyl-D-aspartic acid (NMDA) in 0 Mg2+, and L-glutamate. Each of these caused a depolarization of the cell membrane, a reduction in cell membrane resistance, and the onset of spontaneous firing. 3. Short-latency excitatory postsynaptic potentials (EPSPs) were evoked by stimulation of the lateral lemniscus in 77% of the neurons tested. The mean latency to initial depolarization was 0.9 ms. A single spike with relatively constant latency (mean 1.5 ms) was typically elicited when the strength of lemniscal stimulation was increased. A longer-latency EPSP (mean 2.9 ms) was seen in 34% of the neurons tested either with the slice in normal saline or after pharmacological block of the earlier, short-latency EPSP. The long-latency EPSP was followed by a single spike of multiple spikes with highly variable latencies (range 3.2-24 ms). In 28% of the neurons tested, both early and late EPSPs were observed in response to stimulation of a single location on the lateral lemniscus. 4. Stimulation of the commissure of Probst elicited short-latency EPSPs (mean 0.9 ms) in 37% of the neurons tested. Longer-latency EPSPs (mean 3.0 ms) were found in only 3% of the neurons in response to commissural stimulation. 5. The nonspecific EAA antagonist kynurenic acid blocked both short-and long-latency EPSPs evoked by either lemniscal or commissural stimulation. The non-NMDA antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), at very low concentrations, blocked the short-latency EPSPs but had no effect on the longer-latency EPSPs. The short-latency EPSPs were unaffected by the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (APV). In contrast, the longer-latency EPSPs were blocked by APV, but never by CNQX. 6. DNLL neurons were affected by the inhibitory amino acid agonists gamma-aminobutyric acid (GABA) and glycine. The membrane resistance of the neurons was decreased by GABA and glycine in a solution of either normal or calcium-free saline in a concentration-dependent manner. 7. Inhibitory postsynaptic potentials (IPSPs) were elicited by stimulation of the lateral lemniscus in 53% of the neurons and the commissure of the Probst in 18% of the neurons tested. The mean latencies were 1.0 and 0.9 ms, respectively. The reversal potentials of the IPSPs were around -70 mV. 8. The IPSPs evoked by stimulation of the lateral lemniscus were blocked by the glycine receptor antagonist strychnine, but not by the GABA receptor antagonist bicuculline, whereas the IPSPs elicited by stimulation of the commissure of Probst were blocked by bicuculline but not strychnine.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1986

Distribution and morphology of tegmental neurons receiving nigral inhibitory inputs in the cat: an intracellular HRP study.

Intracellular recordings and morphological identification of neurons by means of intracellular HRP staining were performed in the midbrain-pontine tegmentum of the cat. Electrical stimulation of the substantia nigra, pars reticulata, induced short-latency inhibitory postsynaptic potentials in tegmental neurons, as previously reported. These tegmental neurons were distributed not only in the pedunculopontine tegmental nucleus (PPTN) (26 cells), but also in the cuneiform nucleus (CNF) (13 cells), the central gray substance (CG) (four cells), the parabrachial nucleus (three cells), and the tegmentum between the inferior colliculus and the CG (two cells). The morphological characteristics of the HRP-stained tegmental neurons were analyzed by camera lucida drawings of 16 well-stained cells, i.e., ten PPTN neurons, three CNF neurons, two neurons in the tegmentum between the IC/CG, and one CG neuron. All of these neurons seem to be classified as "isodendritic" neurons. Regardless of the soma size (15-120 micron in diameter), most of the tegmental neurons showed wide dendritic fields of 1-2 mm, mediolaterally, and 0.5-1 mm, dorsoventrally. These results indicate that the nigrotegmental projections exert an inhibitory influence on the neurons located in a wide variety of nuclei of the midbrain-pontine dorsal tegmentum.

Animals↗

PubMed1983

On the central pattern generator for the basic breathing rhythmicity.

Recent advances in several laboratories concerning the respiration-related medullary neurons, their locations, projections, interconnections, morphological and physiological properties, and patterns of inhibitory postsynaptic potentials, excitatory postsynaptic potentials, and discharge rate, on the one hand, and the "systems behavior," on the other, have provided the basis for new hypothesis concerning the neural mechanisms underlying the central pattern generator (CPG) for breathing and its different parts. The onset of the "ramp"-like increase in inspiratory activity is due to an abrupt release of inhibition and a subsequent progressively increasing synaptic excitation of inspiratory premotor neurons. The integration of the excitatory "drive" inputs underlying the ramp inspiratory activity seems to depend on structures in the ventrorostral medulla, including nucleus paragigantocellularis. The termination of this activity by the off-switch mechanisms is actuated when a critical threshold is attained by the excitatory inputs of 1) a slowly increasing inspiration-related activity and 2) the afferent input from the pulmonary stretch receptors. The nature of the former activity is discussed. During the expiratory phase, an inhibitory activity suppresses inspiration-facilitating inputs with a slowly decaying power that controls the expiratory duration. The postinspiration activity, which brakes the rate of exhalation during the first part of the expiratory phase, depends on mechanisms separate from those responsible for the inspiratory ramp activity. The respiratory CPG seems to be organized with considerable amount of redundancy, or "degeneracity."

Biomechanical Phenomena↗

PubMed1998

Generation of theta and gamma rhythms in the hippocampus.

In the behaving rat, theta rhythm was dominant during walking and rapid-eye-movement sleep, while irregular slow activity predominated during immobility and slow-wave sleep. Oscillatory evoked potentials of 20-50 Hz and spontaneous fast (gamma) waves were more prominent during theta compared with non-theta behaviors. The oscillations were simulated by a systems model with recurrent inhibition. The model also predicts a behaviorally dependent inhibition, which was confirmed experimentally using paired-pulse responses. Paired-pulse facilitation (PPF) of the population spikes in CA1 was larger during walking than immobility, mostly mediated by a cholinergic input. Spike responses in vitro were characterized by a relative lack of inhibition or disinhibition compared with the behaving rat. The two-input, two-dipole model of the theta rhythm in CA1 is reviewed. Afferents to the CA1 pyramidal cells are assumed to be rhythmic and consist of atropine-sensitive and atropine-resistant inputs driving the somata and distal dendrites, respectively. The atropine-sensitive theta rhythm was mainly caused by a series of Cl- mediated inhibitory postsynaptic potentials (IPSPs) on pyramidal cells. It is suggested that previous claims of the participation of excitatory postsynaptic potentials (EPSPs) and not IPSPs in the intracellular recordings in vivo were flawed. Single cell recordings in vitro suggested that intrinsic voltage-dependent membrane potential oscillations modulate the response to a theta-frequency driving. Membrane potentials of pyramidal cells in vitro showed resonance in the theta frequency range.

Animals↗

PubMed1979

The roles of endogenous membrane properties and synaptic interaction in generating the heartbeat rhythm of the leech, Hirudo medicinalis.

1. Inhibitory synapses among the central neurones involved in the generation of the heartbeat rhythm of the leech were blocked by either low Cl- physiological saline or presynaptic hyperpolarizing current. 2. Low Cl- saline reversibly blocked inhibitory postsynaptic potentials (IPSPs) from the HN cells onto both other HN cells and HE cells but did not block electrical coupling among HN cells. 3. The rhythmic bursts of impulses in HE cells were abolished when IPSPs were blocked by either low Cl- saline or hyperpolarization of HN cells. 4. The rhythmic bursts of impulses in HN cells were not abolished (except in cell HN(5)) when IPSPs were blocked by low Cl- saline, but phase relations became unfixed (unless the cells were electrically coupled). 5. Both brief depolarizing and hyperpolarizing current pulses reset the rhythm of HN cells whose IPSPs were blocked by low Cl- saline. 6. The results indicate that the motor neurones to the heart (HE cells) produce rhythmic impulse bursts because their steady discharge is periodically inhibited by the HN interneurones. The pattern generated by the HN cells originates from an endogenous rhythm co-ordinated by the inhibitory interactions and electrical coupling between these cells.

Action Potentials↗

PubMed1997

Dynamic interactions determine partial thalamic quiescence in a computer network model of spike-and-wave seizures.

In vivo intracellular recording from cat thalamus and cortex was performed during spontaneous spike-wave seizures characterized by synchronously firing cortical neurons correlated with the electroencephalogram. During these seizures, thalamic reticular (RE) neurons discharged with long spike bursts riding on a depolarization, whereas thalamocortical (TC) neurons were either entrained into the seizures (40%) or were quiescent (60%). During quiescence, TC neurons showed phasic inhibitory postsynaptic potentials (IPSPs) that coincided with paroxysmal depolarizing shifts in the simultaneously recorded cortical neuron. Computer simulations of a reciprocally connected TC-RE pair showed two major modes of TC-RE interaction. In one mode, a mutual oscillation involved direct TC neuron excitation of the RE neuron leading to a burst that fed back an IPSP into the TC neuron, producing a low-threshold spike. In the other, quiescent mode, the TC neuron was subject to stronger coalescing IPSPs. Simulated cortical stimulation could trigger a transition between the two modes. This transition could go in either direction and was dependent on the precise timing of the input. The transition did not always follow the stimulation immediately. A larger, multicolumnar simulation was set up to assess the role of the TC-RE pair in the context of extensive divergence and convergence. The amount of TC neuron spiking generally correlated with the strength of total inhibitory input, but large variations in the amount of spiking could be seen. Evidence for mutual oscillation could be demonstrated by comparing TC neuron firing with that in reciprocally connected RE neurons. An additional mechanism for TC neuron quiescence was assessed with the use of a cooperative model of gamma-aminobutyric acid-B (GABA(B))-mediated responses. With this model, RE neurons receiving repeated strong excitatory input produced TC neuron quiescence due to burst-duration-associated augmentation of GABA(B) current. We predict the existence of spatial inhomogeneity in apparently generalized spike-wave seizures, involving a center-surround pattern. In the center, intense cortical and RE neuron activity would be associated with TC neuron quiescence. In the surround, less intense hyperpolarization of TC neurons would allow low-threshold spikes to occur. This surround, an "epileptic penumbra," would be the forefront of the expanding epileptic wave during the process of initial seizure generalization. Therapeutically, we would then predict that agents that reduce TC neuron activity would have a greater effect on seizure onset than on ongoing spike-wave seizures or other thalamic oscillations.

Action Potentials↗

PubMed2002

Effects of dynorphin on rat entopeduncular nucleus neurons in vitro.

The entopeduncular nucleus (EP) receives dense neostriatal afferent axons that contain dynorphin (DYN, an endogenous kappa-receptor agonist), in addition to GABA and substance P. To examine the role of DYN in the EP, whole-cell recordings were performed in rat brain slice preparations. Based on the physiological and morphological characteristics, all the neurons recorded were similar to the Type-I EP neuron described in a previous study. The kappa-receptor agonist dynorphin A (1-13) (DYN13) hyperpolarized and decreased the input resistance of approximately one-quarter of the EP neurons examined. The hyperpolarization was due to an increase in potassium conductance since current-voltage relationship curves obtained before and after DYN13 application crossed at the potassium equilibrium potential. In the presence of the glutamate blocker 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide and 3-(2-carboxypiperzin-4-yl)-propyl-1-phosphonic acid in artificial cerebrospinal fluid, stimulation of the globus pallidus evoked bicuculline-sensitive multi-component GABAergic responses in EP neurons. Application of DYN13 equally reduced the amplitudes of the short-latency response, conceivably evoked by pallido-EP axons, and the medium-latency response, conceivably evoked by striato-EP axons. These effects were reversed by bath application of a non-selective opioid antagonist naloxone or by a kappa-opioid receptor-selective antagonist nor-binaltorphimine dihydrochloride (nor-BNI), but not by the partial differential -antagonist naltrindole or the mu-antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2). DYN13 also reduced the frequency of tetrodotoxin-insensitive miniature-inhibitory postsynaptic potential (mIPSPs) without changing their amplitude distributions. The decrease of the frequency of mIPSPs was reversible upon washing and was also completely blocked by nor-BNI. The results of the present study on the EP indicated that DYN released from striatal axons might exert at least three different effects on these target nuclei. Firstly, DYN might provide negative feedback regulation of striatal GABAergic outputs at their termination sites. Secondly, DYN released from the striatal terminals might diffuse to the pallidal terminals, regulating their GABA release. Thirdly, DYN might exert a direct inhibition of EP neurons. Thus, DYN released from striatal axons might control the activity of EP neurons by reducing the GABAergic transmission and also by hyperpolarizing postsynaptic membrane.

Anesthetics, Local↗

PubMed1995

Segment-specific effects of FMRFamide on membrane properties of heart interneurons in the leech.

1. The effects of Phe-Met-Arg-Phe (FMRF)amide (10(-6) M) on membrane properties of heart interneurons in the third, fourth, and fifth segmental ganglia [HN(3), HN(4), and HN(5) cells, respectively] of the leech were studied using discontinuous current-clamp and single-electrode voltage-clamp techniques. FMRFamide was focally applied onto the soma of the cell under investigation. 2. Application of FMRFamide depolarized HN(3) and HN(4) cells by evoking an inward current. These responses were subject to pronounced desensitization. The inward currents evoked by application of FMRFamide were associated with an increase in membrane conductance and appeared to be voltage dependent. Currents were enhanced at more depolarized potentials. 3. The responsiveness of the HN(3) and HN(4) cells was not affected when the Ca2+ concentration in the bath saline was reduced from normal (1.8 mM) to 0.1 mM. The depolarizing response on application of FMRFamide was blocked when Co2+ was substituted for Ca2+. 4. HN(3) and HN(4) cells did not respond to FMRFamide application in Na(+)-free solution. Inward currents were largely reduced when bath saline with 30% of the normal Na+ concentration was used. When Li+ was substituted for Na+ in the saline, application of FMRFamide still evoked depolarizing responses in HN(3) and HN(4) cells. 5. We conclude that focal application of FMRFamide onto the somata of HN(3) and HN(4) cells evokes a voltage-dependent inward current, carried largely by Na+. 6. Focal application of FMRFamide onto somata of HN(5) cells hyperpolarized these cells by activating a voltage-dependent outward current. 7. HN(5) cells were loaded with Cl- until inhibitory postsynaptic potentials carried by Cl- reversed. Cl(-)-loaded cells still responded with a hyperpolarization when FMRFamide was applied onto their somata. Therefore the outward current evoked by FMRFamide appears to be mediated by a K+ conductance increase. 8. Application of FMRFamide onto the somata of HN(5) cells enhanced outward currents that were evoked by depolarizing voltage steps from a holding potential of -45 mV. 9. We conclude that the hyperpolarizing response of HN(5) cells to focal application of FMRFamide onto their somata is the result of an up-regulation of a voltage-dependent K+ current.

Animals↗

PubMed1995

Serotonin reduces inhibition via 5-HT1A receptors in area CA1 of rat hippocampal slices in vitro.

We studied the effects of serotonin (5-HT) on intrinsic and synaptic responses of hippocampal CA1 cells. The effects were partially mimicked by the 5-HT1A receptor agonist, 8-OH-DPAT, and prevented by the 5-HT1A receptor antagonist, NAN-190. Polysynaptic fast and slow inhibitory postsynaptic potentials (IPSPs) were reduced in amplitude by 60-70% following application of both 5-HT and 8-OH-DPAT. Monosynaptic fast IPSPs were reduced by 60% and slow IPSPs by 90% following application of both drugs. Since there is a temporal overlap of fast and slow IPSPs, the reduction in fast IPSPs could have arisen indirectly from the larger effect of 5-HT on slow IPSPs. To overcome this problem we blocked the slow IPSPs with new, potent GABA-B antagonists, but still observed a similar reduction in the fast IPSP with 5-HT and 8-OH-DPAT. However, the reductions in the fast IPSPs could also have arisen from the 5-HT-induced total conductance increases. Using single-electrode voltage clamp and intracellular K+ channel blockers we still observed similar changes. 5-HT and 8-OH-DPAT had no effect upon GABA-A-mediated currents evoked by iontophoretic GABA application to the dendrites or the soma of CA1 pyramidal cells, Putative inhibitory internuerons were hyperpolarized by 5-HT and their evoked EPSPs strongly reduced by 5-HT and 8-OH-DPAT. Our data indicate that 5-HT modulates fast and slow synaptic inhibition of principal cells using presynaptic mechanisms involving the inhibition of inhibitory interneurons.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1994

Spatiotemporally differential inhibition of pyramidal cells in the cat motor cortex.

1. The spatiotemporal pattern of inhibition in the cat motor cortex was studied in in vitro slice preparations in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonovaleric acid (APV). 2. After intracortical microstimulation (0.5-6 microA), fast and slow inhibitory postsynaptic potentials (IPSPs) were produced in layers II-VI pyramidal cells and selectively reduced with bicuculline methiodide and phaclofen, respectively. 3. Fast IPSPs were maximally produced by stimulation of the same layer where their cell bodies were located, and they decreased in amplitude as the more superficial layer was stimulated. In contrast, slow IPSPs were maximally produced by stimulation of layer II regardless of the location of the recorded pyramidal cell and decreased in amplitude as the deeper layer was stimulated. 4. The reduction of amplitude of fast IPSPs, in response to a vertical shift of the stimulation site toward more superficial layers, was always correlated with an increase in rise time and with a shift of the reversal potential to a more hyperpolarized level. 5. When the stimulation site was moved horizontally to the more lateral site, fast IPSPs increased in latency and decreased in amplitude gradually without appreciable changes in rise time. Fast IPSPs could be evoked from horizontally remote sites of up to 800-1,200 microns. 6. Inhibitory interneurons, which are responsible for evoking fast IPSPs, appear to be distributed through almost all layers to send horizontally spreading parallel axons making synaptic contacts at different electrotonic distances along apical dendrites of single pyramidal cells. 7. Horizontal spreads were much less in slow IPSPs (< 340-680 microns). The time-to-peak of slow IPSPs produced in layer V pyramidal cells (159.5 +/- 6.8 ms, mean +/- SD, n = 10) was significantly (P < 0.0001) longer than that in layers II and III pyramidal cells (128.5 +/- 7.5 ms, n = 7). Asymmetric reversal properties of slow IPSPs were seen, suggesting the spatial dispersion of synaptic inputs along apical dendrites of pyramidal cells. 8. In layer V pyramidal cells, the time-to-peak of slow IPSPs decreased with increasing membrane hyperpolarization, indicating that the later portion of slow IPSPs was more sensitive to the membrane-potential change than the early portion. This further indicates that the late portion of slow IPSPs is generated at synapses on the more proximal dendrite of pyramidal cells than the early portion, contrary to that expected from the Rall's model of passive dendrite under the condition of synchronous inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1999

Naloxone reduces the amplitude of IPSPs evoked in lumbar motoneurons by reticular stimulation during carbachol-induced motor inhibition.

During active sleep or carbachol-induced motor inhibition, electrical stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) evoked large amplitude, glycinergic inhibitory postsynaptic potentials (IPSPs) in cat motoneurons. The present study was directed to determine whether these IPSPs, that are specific to the state of active sleep, are modulated by opioid peptides. Accordingly, intracellular recordings were obtained from lumbar motoneurons of acute decerebrate cats during carbachol-induced motor inhibition while an opiate receptor antagonist, naloxone, was microiontophoretically released next to the recorded cells. Naloxone reversibly reduced by 26% the mean amplitude of NRGc-evoked IPSPs (1.9+/-0.2 mV (S.E.M.) vs. 1.4+/-0.2 mV; n=11, control and naloxone, respectively, p<0.05), but had no effect on the other waveform parameters of these IPSPs (e.g., latency-to-onset, latency-to-peak, duration, etc.). The mean resting membrane potential, input resistance and membrane time constant of motoneurons following naloxone ejection were not statistically different from those of the control. These data indicate that opioid peptides have a modulatory effect on NRGc-evoked IPSPs during carbachol-induced motor inhibition. We therefore suggest that endogenous opioid peptides may act as neuromodulators to regulate inhibitory glycinergic synaptic transmission at motoneurons during active sleep.

Animals↗

PubMed1990

Bicuculline- and Phaclofen-Resistant Hyperpolarizations Evoked by Glutamate Applications to Stratum Lacunosum-Moleculare in CA1 Pyramidal Cells of the Rat Hippocampus In Vitro.

In the hippocampus, different types of interneurons may mediate distinct gamma-aminobutyric acid (GABA) responses, i.e. the early and late inhibitory postsynaptic potentials (IPSPs). To verify this hypothesis, intracellular recordings were obtained from CA1 pyramidal cells (n=63) in rat hippocampal slices. Glutamate (1 mM) was locally ejected in stratum lacunosum-moleculare to activate interneurons in this region. Glutamate-evoked hyperpolarizing responses were characterized in pyramidal cells and compared to the early IPSP and the late IPSP elicited by stratum radiatum electrical stimulation. Several characteristics were similar for the glutamate-evoked IPSPs and late IPSPs: their amplitude was small (-3.4 versus -4.9 mV, respectively), each was associated with a small conductance increase (5.0 versus 9.3 nS, respectively), their peak latency was slow (124.4 versus 129.8 ms, respectively) and in the majority of cells, each displayed little response reversal. However, the equilibrium potential of the glutamate IPSP (-76.5 mV) was similar to that of the early IPSP (-73.8 mV). Perfusion with a low Ca2+ (0.5 mM)/high Mg2+ (8 mM) medium or with tetrodotoxin (1 microM), which blocked synaptic transmission, also reduced the glutamate IPSP. Therefore the glutamate IPSP may be mediated indirectly by inhibitory interneurons. The GABAA antagonist bicuculline (10 microM), or picrotoxin (10-20 microM), blocked the early IPSP, but not the glutamate IPSP. The GABAB antagonist phaclofen (1 mM) attenuated the late IPSP, but did not affect the glutamate IPSP. The results of these experiments suggest that glutamate stimulation of interneurons in stratum lacunosum-moleculare evokes a slow IPSP different from the GABA-mediated early and late IPSPs in CA1 pyramidal cells of the hippocampus.

Journal Article↗

PubMed1987

Inputs from regularly and irregularly discharging vestibular nerve afferents to secondary neurons in the vestibular nuclei of the squirrel monkey. II. Correlation with output pathways of secondary neurons.

1. Intracellular recordings were made from secondary neurons in the vestibular nuclei of barbiturate-anesthetized squirrel monkeys. Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the ipsilateral vestibular nerve (Vi) were measured. An electrophysiological paradigm, described in the preceding paper (26), was used to determine the proportion of irregularly (I) and regularly (R) discharging Vi afferents making direct connections with individual secondary neurons. The results were expressed as a % I index, an estimate for each neuron of the percentage of the total Vi monosynaptic input that was derived from I afferents. The secondary neurons were also classified as I, R, or M cells, depending on whether they received their direct Vi inputs predominantly from I or R afferents or else from a mixture (M) of both kinds of Vi fibers. The neurons were located in the superior vestibular nucleus (SVN) or in the rostral parts of the medical or lateral (LVN) vestibular nuclei. 2. Antidromic activation or reconstruction of axonal trajectories after intrasomatic injection of horseradish peroxidase (HRP) was used to identify three classes of secondary neurons in terms of their output pathways: 1) cerebellar-projecting (Fl) cells innervating the flocculus (n = 26); 2) rostrally projecting (Oc) cells whose axons ascended toward the oculomotor (IIIrd) nucleus (n = 27); and 3) caudally projecting (Sp) cells with axons descending toward the spinal cord (n = 13). Two additional neurons, out of 21 tested, could be antidromically activated both from the level of the IIIrd nucleus and from the spinal cord. 3. The Vi inputs to the various classes of relay neurons differed. As a class, Oc neurons received the most regular inputs. Sp neurons had more irregular inputs. Fl neurons were heterogeneous with similar numbers of R, M, and I neurons. The mean values (+/- SD) of the % I index for the Oc, Fl, and Sp neurons were 34.7 +/- 24.7, 51.9 +/- 30.4, and 61.8 +/- 18.0%, respectively. Only the Oc neurons had a % I index that was similar to the proportion of I afferents (34%) in the vestibular nerve (cf. Ref. 26). 4. The commissural inputs from the contralateral vestibular nerve (Vc) also differed for the three projection classes. Commissural inhibition was most common in Fl cells: 22/25 (88%) of the neurons had Vc inhibitory postsynaptic potentials (IPSPs) and 1/25 (4%) had a Vc EPSP. In contrast, Vc inputs were only observed in approximately half the Oc and Sp neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1991

Postnatal development of neuronal connections in cat visual cortex studied by intracellular recording in slice preparation.

Postnatal development of neuronal connections in cat visual cortex (area 17) was studied in slice preparations obtained from kittens aged 1-18 weeks after birth and adult cats by recording intracellularly excitatory (EPSP) and inhibitory postsynaptic potentials (IPSP) evoked in cortical cells by stimulation of white matter. The EPSPs were already present in all cells at 1 week of age. Their efficiency assessed by their maximum rate of rise was low initially and increased progressively with age. In contrast, the IPSPs were absent in half of the cells at 1 week and almost all of the cells came to demonstrate inhibition by 9 weeks except for a few layer II-III cells. At all ages about three-quarters of the IPSPs had GABAA-mediated early and GABAB-mediated late components with different time courses, reversal potential and sensitivity to GABA antagonists, while the remaining IPSPs had only the early component. The efficiency of both IPSPs assessed by the associated conductance increase showed an increase of more than twice from 1 to 5 weeks, reaching the same level as adults. The time course of the development of inhibition demonstrated in this study paralleled the time course of the development of selective visual responsiveness in cortical cells, suggesting that the postnatal maturation of inhibitory connections is a basis of maturation of visual responsiveness.

Aging↗

PubMed1997

Recruitment of GABAergic inhibition and synchronization of inhibitory interneurons in rat neocortex.

Intracellular recordings were obtained from pyramidal and interneuronal cells in rat neocortical slices to examine the recruitment of GABAergic inhibition and inhibitory interneurons. In the presence of the convulsant agent 4-aminopyridine (4-AP), after excitatory amino acid (EAA) ionotropic transmission was blocked, large-amplitude triphasic inhibitory postsynaptic potentials (IPSPs) occurred rhythmically (every 10-40 s) and synchronously in pyramidal neurons. After exposure to the gamma-aminobutyric acid-A (GABA(A)) receptor antagonist picrotoxin, large-amplitude monophasic slow IPSPs persisted in these cells. In the presence of 4-AP and EAA blockers, interneurons showed periodic spike firing. Although some spikes rode on an underlying synaptic depolarization, much of the rhythmic firing consisted of spikes having highly variable amplitudes, arising abruptly from baseline, even during hyperpolarization. The spike firing and depolarizing synaptic potentials were completely suppressed by picrotoxin exposure, although monophasic slow IPSPs persisted in interneurons. This suggests that this subset of interneurons may participate in generating fast GABA(A) IPSPs, but not slow GABA(B) IPSPs. Cell morphology was confirmed by intracellular injection of neurobiotin or the fluorescent dye Lucifer yellow CH. Dye injection into interneurons often (>70%) resulted in the labeling of two to six cells (dye coupling). These findings suggest that GABA(A)ergic neurons may be synchronized via recurrent collaterals through the depolarizing action of synaptically activated GABA(A) receptors and a mechanism involving electrotonic coupling. Although inhibitory neurons mediating GABA(B) IPSPs may be entrained by the excitatory GABA(A) mechanism, they appear to be a separate subset of GABAergic neurons capable of functioning independently with autonomous pacing.

Animals↗

PubMed2001

Regulation of a G protein-gated inwardly rectifying K+ channel by a Ca(2+)-independent protein kinase C.

1. Members of the Kir3.0 family of inwardly rectifying K(+) channels are expressed in neuronal, atrial and endocrine tissues and play key roles in generating late inhibitory postsynaptic potentials (IPSPs), slowing heart rate and modulating hormone release. They are activated directly by G(betagamma) subunits released in response to G(i/o)-coupled receptor stimulation. However, it is not clear to what extent this process can be dynamically regulated by other cellular signalling systems. In this study we have explored pathways activated by the G(q/11)-coupled M(1) and M(3) muscarinic receptors and their role in the regulation of Kir3.1+3.2A neuronal-type channels stably expressed in the human embryonic kidney cell line HEK293. 2. We describe a novel biphasic pattern of behaviour in which currents are initially stimulated but subsequently profoundly inhibited through activation of M(1) and M(3) receptors. This contrasts with the simple stimulation seen through activation of M(2) and M(4) receptors. 3. Channel stimulation via M(1) but not M(3) receptors was sensitive to pertussis toxin whereas channel inhibition through both M(1) and M(3) receptors was insensitive. In contrast over-expression of the C-terminus of phospholipase Cbeta1 or a G(q/11)-specific regulator of G protein signalling (RGS2) essentially abolished the inhibitory phase. 4. The inhibitory effects of M(1) and M(3) receptor stimulation were mimicked by phorbol esters and a synthetic analogue of diacylglycerol but not by the inactive phorbol ester 4alphaphorbol. Inhibition of the current by a synthetic analogue of diacylglycerol effectively occluded any further inhibition (but not activation) via the M(3) receptor. 5. The receptor-mediated inhibitory phenomena occur with essentially equal magnitude at all intracellular calcium concentrations examined (range, 0-669 nM). 6. The expression of endogenous protein kinase C (PKC) isoforms in HEK293 cells was examined by immunoblotting, and their translocation in response to phorbol ester treatment by cellular extraction. The results indicated the expression and translocation of the novel PKC isoforms PKCdelta and PKCepsilon. 7. We also demonstrate that activation of such a pathway via both receptor-mediated and receptor-independent means profoundly attenuated subsequent channel stimulation by G(i/o)-coupled receptors. 8. Our data support a role for a Ca(2+)-independent PKC isoform in dynamic channel regulation, such that channel activity can be profoundly reduced by M(1) and M(3) muscarinic receptor stimulation.

Carbachol↗

PubMed1997

Presynaptic modulation by metabotropic glutamate receptors of excitatory and inhibitory synaptic inputs to hypothalamic magnocellular neurons.

The effects of activation of metabotropic glutamate receptors (mGluRs) on synaptic inputs to magnocellular neurons of the hypothalamic supraoptic nucleus (SON) were studied with the use of whole cell patch-clamp and microelectrode recordings in acute hypothalamic slices. Application of the mGluR agonist trans-(+/-)-1-amino-1,3-cyclopentane dicarboxylic acid (trans-ACPD, 100 microM) elicited an increase in the frequency of spontaneous excitatory postsynaptic potentials (EPSPs) and excitatory postsynaptic currents (EPSCs) in 20% of the cells, and of spontaneous inhibitory postsynaptic potentials (IPSPs) and inhibitory postsynaptic currents (IPSCs) in 50% of the cells tested in normal medium. The increased frequency of spontaneous EPSPs/EPSCs and IPSPs/IPSCs was blocked by tetrodotoxin (TTX), indicating that mGluRs act to excite the somata/dendrites of presynaptic glutamatergic and GABAergic neurons. (RS)-3,5-dihydroxyphenylglycine (50 microM), a selective group I receptor agonist, mimicked the presynaptic somatic/dendritic effects of trans-ACPD, suggesting that the presynaptic somatic/dendritic receptors responsible for increased spike-dependent glutamate and gamma-aminobutyric acid (GABA) release belong to the group I mGluRs. In the presence of TTX, trans-ACPD caused a decrease in the frequency of miniature EPSCs (up to 90%) in 13 of 16 cells, and a decrease in the frequency of miniature IPSCs (up to 80%) in 10 of 16 cells tested. Miniature EPSC and IPSC amplitudes usually did not change in trans-ACPD, suggesting that activation of metabotropic receptors located at presynaptic glutamatergic and GABAergic terminals led to a reduction in transmitter release onto SON magnocellular neurons. L(+)-2-amino-4-phosphonobutyric acid (100-250 microM), a selective group III receptor agonist, mimicked the effects of trans-ACPD at presynaptic terminals, decreasing the frequency of miniature EPSCs and IPSCs by up to 85% without affecting their amplitude. Thus the metabotropic receptors at presynaptic glutamate and GABA terminals in the SON belong to group III mGluRs. EPSCs evoked by electrical stimulation were enhanced by the group III receptor antagonist (S)-2-amino-2-methyl-4-phosphonobutanoic acid, suggesting that presynaptic metabotropic receptors are activated by the release of endogenous glutamate. These data indicate that mGluRs in the hypothalamus have opposing actions at presynaptic somata/dendrites and at presynaptic terminals. Activation of group I receptors (mGluR1 and/or mGluR5) on presynaptic somata/dendrites led to an increase in spike-dependent transmitter release, whereas activation of the group III receptors (mGluR4, 7, and/or 8) on presynaptic terminals suppressed glutamate and GABA release onto SON neurons. No differences were seen in the effects of mGluR activation between immunohistochemically identified oxytocin and vasopressin neurons of the SON.

Animals↗

PubMed1999

Regulation of the rebound depolarization and spontaneous firing patterns of deep nuclear neurons in slices of rat cerebellum.

Current-clamp recordings were made from the deep cerebellar nuclei (DCN) of 12- to 15-day-old rats to understand the factors that mediate intrinsic spontaneous firing patterns. All of the cells recorded were spontaneously active with spiking patterns ranging continuously from regular spiking to spontaneous bursting with the former predominating. A robust rebound depolarization (RD) leading to a Na(+) spike burst was elicited after the offset of hyperpolarizing current injection. The voltage and time dependence of the RD was consistent with mediation by low-threshold voltage-gated Ca(2+) channels. In addition, induction of a RD also may be affected by activation of a hyperpolarization-activated cation current, I(h). A RD could be evoked efficiently after brief high-frequency bursts of inhibitory postsynaptic potentials (IPSPs) induced by stimulation of Purkinje cell axons. IPSP-driven RDs were typically much larger and longer than those elicited by direct hyperpolarizing pulses of approximately matched amplitude and duration. Intracellular perfusion of the Ca(2+) buffer bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) dramatically enhanced the RD and its associated spiking, sometimes leading to a plateau potential that lasted several hundred milliseconds. The effects of BAPTA could be mimicked partly by application of apamin, a blocker of small conductance Ca(2+)-gated K(+) channels, but not by paxilline, which blocks large conductance Ca(2+)-gated K(+) channels. Application of both BAPTA and apamin, but not paxilline, caused cells that were regularly spiking to burst spontaneously. Taken together, our data suggest that there is a strong relationship between the ability of DCN cells to elicit a RD and their tendency burst spontaneously. The RD can be triggered by the opening of T-type Ca(2+) channels with an additional contribution of hyperpolarization-activated current I(h). RD duration is regulated by small-conductance Ca(2+)-gated K(+) channels. The RD also is modulated tonically by inhibitory inputs. All of these factors are in turn subject to alteration by extrinsic modulatory neurotransmitters and are, at least in part, responsible for determining the firing modes of DCN neurons.

Anesthetics, Local↗