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W H Griffith

Publications and source records attributed to W H Griffith.

At least 37 records · Page 2Linked to original sources
PubMed1991

Electrophysiologic characteristics of basal forebrain neurons in vitro.

Our data show that different cell types recorded in vitro can be identified by their intrinsic membrane properties. One type of neuron, namely S-AHP cells, have the ability to fire single action potentials in a rhythmic fashion following sufficient membrane depolarization. The rate is apparently controlled by several voltage-dependent conductances. S-AHP cells are normally quiescent at their resting potentials but will discharge once threshold is reached (-55 to -60 mV). Importantly, S-AHP (or F-AHP) cells will not convert into burst-firing neurons merely with changes in membrane potential. On the other hand, burst-firing cells have the ability to switch to a repetitive-firing pattern following membrane depolarization. All of these data provide a first step in an understanding of the firing rates of basal forebrain neurons, however, our results must be consolidated with existing in vivo studies for a more general understanding of basal forebrain function. Comparing our data to an in vivo preparation of the MS/nDB with synaptic afferents surgically removed may be one approach to correlating in vitro and in vivo studies. Vinogradova et al. (1980) used single unit recording techniques in unanesthetized chronic rabbits and compared the firing rates of cells before and after deafferentation. These authors reported a preservation of burst-firing neurons (25% of the cells) after deafferentation but with a significant reduction in the mean frequency of bursts. In addition a higher percentage of regularly firing cells also occurred following deafferentation (Vinogradova et al., 1980). It is interesting to speculate that these regularly firing cells may correspond to S-AHP cells in our in vitro studies, and some of the burst-firing units may correspond to the burst-firing cells we record in slices. Nevertheless, the in vivo data strongly suggests that endogenous regular spiking as well as rhythmic burst capabilities are present in some MS/nDB cells, however, the firing rates of most MS/nDB neurons are strongly influenced by synaptic afferents (see also Vinogradova et al., 1980; 1987). The endogenous activity in vivo can be explained, in part, by the intrinsic properties elucidated in our in vitro studies. How the synaptic afferents control MS/nDB circuitry and integrative output is premature to speculate without a more thorough understanding of the synaptic mechanisms involved. It is possible that future in vitro studies will help define these mechanisms and again contribute to an understanding of basal forebrain function.

Action Potentials↗
PubMed1990

Membrane currents in hippocampal neurons.

This chapter reviews properties and functions of endogenous ionic currents in hippocampal neurones. Currents considered are: Na currents INa(fast) and INa(slow); Ca currents; K currents--delayed rectifier IK(DR), transient IK(A), 'delay' current IK(D) and M current IK(M); inward rectifiers IQ, IK(IR) and ICl(V); Ca-activated currents IK(Ca) (IC and IAHP), ICl(Ca) and Ication(Ca); Na-activated currents; and anoxia-induced currents.

Animals↗
PubMed1990

Voltage-clamp analysis of posttetanic potentiation of the mossy fiber to CA3 synapse in hippocampus.

1. Short-term changes in synaptic efficacy were studied at the mossy fiber (MF) to CA3 (MF-CA3) synapse in the in vitro hippocampus. Monosynaptic excitatory postsynaptic currents (EPSCs) were recorded before and during posttetanic potentiation (PTP) with the use of intracellular recording and single-electrode voltage-clamp (SEVC) techniques. 2. Repetitive stimulation (100 Hz for 1 s) of the MF synaptic inputs to CA3 pyramidal cells resulted in PTP averaging 170 +/- 19% (SE, n = 42) over control and decaying with a time constant (tau p) of 59.7 +/- 5 s(n = 23). Reproducible episodes of PTP could be recorded if low stimulus intensities were used. Also, after MF tetanization, a faster component, termed augmentation, preceded PTP but could not be accurately resolved within the experimental protocol; only estimates of this component are included. 3. Biophysical parameters of the EPSC that were monitored before and during PTP included synaptic conductance (G), synaptic reversal potential (Erev), decay time constant (tau EPSC), and input resistance of the postsynaptic cell. During PTP the EPSC synaptic conductance increased from 9.8 to 32.7 nS (P less than 0.02, n = 6), whereas there was no statistical change in Erev (-6.0 compared with -6.7 mV, n = 6), tau EPSC (4.3 compared with 4.5 ms, n = 9), or postsynaptic input resistance (59 compared with 63 M omega, n = 12). 4. A presynaptic contribution to PTP was studied directly by observing changes in transmitter release during PTP. Presynaptic mechanisms were assessed by determining the ratio of evoked synaptic excitatory postsynaptic potentials (EPSPs) over the total number of stimuli (EPSP-to-stimuli ratio). The ratio of EPSP to stimuli changed from 0.64 to 0.90 (P less than 0.01, n = 7) during PTP. A reduction in the number of synaptic failures can only be explained by a presynaptic mechanism. No assumptions concerning the statistical distribution of transmitter release were necessary because no statistical parameters were determined. 5. Changes in postsynaptic cell properties do not appear to contribute to PTP studied under the present experimental conditions. Direct stimulation of the postsynaptic neuron via the intracellular recording electrode (20-100 Hz/1 s) failed to produce potentiation of the EPSC; in fact, a slight depression was observed at 50 and 100 Hz direct stimulation. Likewise, the postsynaptic input resistance and synaptic Erev did not change during PTP. 6. The specific N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (APV, 20 microM) had no effect on either the magnitude or duration of PTP.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1990

Comparison of contractile responses of the guinea pig ileum longitudinal muscle to ethanol and GABAA agonists.

The guinea pig ileum myenteric plexus contains GABAA receptors linked to chloride ion channels which are pharmacologically similar to those in the central nervous system. The present study examined the reported ability of acute ethanol treatment to directly activate GABAA receptors or to increase GABAA agonist-mediated activation of the GABAA receptor in the myenteric plexus. Direct addition of ethanol to preparations of the guinea pig ileum longitudinal muscle had two effects. Immediately after ethanol (10-300 mM) was added to the tissue bath a concentration-related contractile response was observed which became maximal within 10 sec and then decayed over the next 60 sec. Contractile responses to higher concentrations of ethanol (greater than 100 mM) also were followed by a sustained reduction of longitudinal muscle tone. Contractions evoked by gamma-aminobutyric acid (GABA) and GABAA agonists, 3-aminopropane sulfonic acid (APSA) (3-100 microM) or muscimol (0.3-30 microM) developed maximally and decayed within 20 sec. Acetylcholine (0.01-10 microM) induced contractions were sustained over several minutes. Preincubation of tissue strips in ethanol (30 mM) for 1 min did not alter concentration relationships for GABA, muscimol or APSA contractile responses. Furthermore, addition of ethanol (10-100 mM) simultaneously with APSA, or 0.5, 2 or 5 min before the addition of APSA, also failed to consistently enhance contractile responses. Ethanol (30 mM) also did not alter desensitization-induced reductions in contractile responses to muscimol (3 microM) caused by preincubation of tissues with muscimol (1 microM). Finally, contractile responses to ethanol and APSA were completely blocked by atropine (0.1 microM) and tetrodotoxin (0.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Comparison of 4-aminopyridine and tetrahydroaminoacridine on basal forebrain neurons.

This study was designed to investigate the ability of 4-aminopyridine (4-AP) and tetrahydroaminoacridine (THA) to reduce several potassium conductances in cells of the medial septum and nucleus of the diagonal band. Intracellular recording and single electrode voltage-clamp techniques were used in an in vitro brain slice preparation. Both 4-AP (100-300 microM) and THA (300 microM) reduced a transient outward current (A-current), whereas only 4-AP increased the release of spontaneous postsynaptic potentials and significantly prolonged action potential duration. High concentrations of THA (1 mM) were needed to significantly increase action potential duration but these levels of THA were still ineffective in eliciting spontaneous postsynaptic potentials. THA (300 microM), but not 4-AP, had the additional effect of reducing time-dependent membrane rectification (Q-current) in one cell type. Our results demonstrate that both cholinergic and non-cholinergic cells are sensitive to pharmacological concentrations of both compounds.

4-Aminopyridine↗
PubMed1988

Sodium valproate decreases synaptic potentiation and epileptiform activity in hippocampus.

The actions of sodium valproate (NaVP) were studied in the in vitro hippocampus using extracellular, intracellular and voltage-clamp recording techniques. In the CA1 region, concentrations of 30-200 microM NaVP reduced the amplitude but not the time course of post-tetanic potentiation (PTP) of dendritic field excitatory postsynaptic potentials (EPSPs). Epileptiform discharges were studied intracellularly in CA3 cells after pharmacological blockade of synaptic inhibition and repeated tetanic stimulation. NaVP (100 microM) blocked evoked paroxysmal depolarizing shift (PDS) discharges through a mechanism of increasing the threshold for burst-firing. When the PDS current was studied under voltage-clamp, application of NaVP (100 microM) resulted in a graded reduction of the PDS waveform. All of the actions of NaVP may result from inhibition of excitatory synaptic transmission following repetitive cell firing. A hypothesis is proposed that NaVP may act to decrease excitatory synaptic potentiation necessary for network synchronization.

Action Potentials↗
PubMed1988

Substance P-mediated membrane currents in voltage-clamped guinea pig inferior mesenteric ganglion cells.

Responses to substance P (SP) and to hypogastric nerve stimulation were recorded from voltage-clamped guinea pig inferior mesenteric ganglion (IMG) neurons, and compared with those to muscarine. Muscarine produced a voltage-dependent inward current accompanied by a reduced input conductance and inhibition of IM a time- and voltage-dependent K+-current (Brown and Adams: Nature 283:673-676, 1980). SP also produced an inward current, accompanied by a fall in input conductance (20 out of 31 cells) or a rise in input conductance (7 out of 31 cells). The fall in input conductance was not accompanied by an inhibition of M-current (unlike frog ganglia: Adams et al.: British Journal of Pharmacology 79:330-333, 1983) or an inhibition of the inward rectifier current (unlike globus pallidus neurons: Stanfield et al.: Nature 315:498-501, 1985). Repetitive hypogastric nerve stimulation (10-20 Hz, 2-10 s) produced a slow inward postsynaptic current lasting 1-3 min, with decreases or increases of input conductance matching those produced by SP. The postsynaptic current did not show a consistent or reproducible change in amplitude on varying the holding potential between -90 and -25 mV. It is concluded that SP and hypogastric stimulation produce complex and variable changes in ionic conductance in IMG neurons.

Animals↗
PubMed1988

Membrane properties of cell types within guinea pig basal forebrain nuclei in vitro.

1. Neurons in the nucleus of the diagonal band of Broca (nDBB) and ventral portion of the medial septum (MS) were studied using intracellular recording and single-electrode voltage clamp (SEVC) techniques in an in vitro brain slice preparation. Cell types could be operationally divided into three categories: cells with a slow postspike afterhyperpolarization (SAHP cell, 40%), neurons with a fast AHP (FAHP cells, 53%), and a third cell group recorded infrequently (7% of the cells) that fired in a burst pattern. Double-labeling techniques have shown that SAHP cells stain positively for acetylcholinesterase (AChE) and are presumably cholinergic (22). The present study provides a more detailed analysis of the passive and active membrane properties of SAHP and FAHP types within these forebrain nuclei. 2. SAHP cells were characterized by a postspike afterhyperpolarization (AHP) with an amplitude of 10-20 mV and duration of approximately 600 ms at -65 mV. In the voltage range of -60--70 mV, the AHP decayed as a single exponential function with a time constant of 170 +/- 53 ms (n = 10). However, many neurons at these membrane potentials exhibited an AHP decay that was a multiple exponential function lasting for seconds. The null potential of the SAHP was approximately -90 mV and shifted by 25 mV in 9 mM KCl, a value closely predicted for a potassium (K+) conductance. The SAHP was reversibly blocked by cadmium (Cd2+), suggesting the SAHP was mediated by a calcium (Ca2+)-activated K+ conductance. 3. FAHP cells displayed afterhyperpolarizations of smaller amplitude (5-10 mV) and duration (5-50 ms) that reversed at approximately -85 mV. Elevating extracellular K+ concentration [Ko] to 6 mM shifted the reversal 13 mV more positive. Cd2+ also reduced the AHP in these cells suggesting a second faster Ca2+-activated K+ conductance may be present. 4. Both SAHP and FAHP cells had similar input resistances and resting membrane potentials but markedly different action-potential characteristics. SAHP cells had a spike duration of 1.4 ms and a prominent shoulder on the falling phase of the SAHP cell action potentials that was reduced by Cd2+. In contrast, FAHP cells had an average spike duration of 0.63 ms that was unaffected by Cd2+. 5. The passive electrical cable properties of both cell types were characterized. Equivalent electrotonic length of the dendrites (L) and the dendritic-to-somatic conductance ratio (rho) were calculated for different cell groups. SAHP cells displayed average L values of 0.61, and the average rho was 2.13. Similar values of 0.69 and 2.14 were calculated for L and rho, respectively, in FAHP cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Phenytoin reduces excitatory synaptic transmission and post-tetanic potentiation in the in vitro hippocampus.

Phenytoin (10-100 microM) was studied on excitatory synaptic transmission and post-tetanic potentiation (PTP) in the in vitro rat hippocampus. Synaptic potentials were studied using extracellular, intracellular and single-electrode voltage clamp techniques. Field excitatory postsynaptic potentials were recorded from the apical dendrites of CA1 pyramidal cells after Schaffer collateral stimulation. Intracellularly recorded excitatory postsynaptic potentials and excitatory postsynaptic currents were recorded in CA3 pyramidal cells after mossy fiber stimulation and in the presence of 10 microM picrotoxinin. In the CA1 region, phenytoin elicited a reversible depression of field excitatory postsynaptic potentials as well as reduced the time constant of decay of PTP from 79 sec to 47 sec with no change in the magnitude of potentiation. Higher concentrations of phenytoin (100 microM) had a general depressant effect on both the amplitude and time course of PTP. In CA3 cells, phenytoin (10 microM) reduced the mossy fiber synaptic conductance but did not change its reversal potential. Phenytoin (10 microM) also reduced the time constant of decay of PTP of the mossy fiber to CA3 synapse, while having no effect on the magnitude of potentiation. These results show that therapeutically relevant concentrations of phenytoin depress both low-frequency synaptic transmission and the time course of short-term potentiation. Both actions may be involved in the anticonvulsant properties of phenytoin.

Animals↗
PubMed1986

Electrophysiology of AChE-positive neurons in basal forebrain slices.

We have utilized a guinea pig in vitro brain slice preparation of the medial septum (MS) and the vertical and horizontal limbs of the nucleus of the diagonal band of Broca (nDBB) to identify and classify different cell types within cholinergic nuclei. Utilizing a double-labeling technique which pairs intracellular injection of the fluorescent dye Lucifer yellow with acetylcholinesterase (AChE) histochemistry, we were able to correlate electrophysiological characteristics with a specific cholinergic cell marker. We report that at least two cell groups can be identified electrophysiologically within the MS/nDBB complex, and one population of neurons demonstrates distinct electrophysiological characteristics that are highly correlated with positive AChE-staining.

Acetylcholinesterase↗
PubMed1986

Voltage-clamp analysis of synaptic inhibition during long-term potentiation in hippocampus.

The excitatory synaptic response evoked by stimulating the mossy fiber synaptic input to hippocampal CA3 neurons in normally accompanied by concomitant feedforward or recurrent inhibition. The purpose of the present study was to determine whether a decrease in the inhibitory conductance of this mixed synaptic response contributes to the enhanced synaptic efficacy observed during long-term potentiation (LTP). Intracellular recordings were made from CA3 neurons of rat hippocampal brain slices. Current- and voltage-clamp measurements of the mixed excitatory/inhibitory evoked synaptic response were made, using a single-electrode clamp system. Outward and inward rectification were reduced, respectively, by intracellular injection and bath application of Cs+. Biophysical analysis of the evoked synaptic conductance sequence was performed before and 15 min to 1 h after inducing LTP. As expected, measurements made in the early part of the conductance sequence, which represents primarily the monosynaptic excitatory input, demonstrated an increase in the slope conductance during LTP. Measurements made later in the conductance sequence, when the excitatory component appeared to have declined to a negligible value, revealed no decrease in the slope conductance of the inhibitory component of the mixed response. We conclude that a decrease in the conductance associated with the inhibitory component of the mixed synaptic response plays little or no role in the increase in synaptic efficacy observed during LTP of this synaptic system.

Animals↗
PubMed1983

Calcium-activated outward current in voltage-clamped hippocampal neurones of the guinea-pig.

Slow clamp currents were recorded from CA1 and CA3 pyramidal neurones in slices of guinea-pig hippocampus maintained in vitro, using a single micro-electrode sample-and-hold technique. Depolarizing voltage commands evoked a time- and voltage-dependent outward current which was suppressed by removing external Ca or by adding Cd (0.5 mM) or Mn (5 mM). This Ca-dependent current (Ic) was not reduced by muscarinic agonists (unlike IM) but was greatly reduced by 5-20 mM-tetraethylammonium (TEA). Repolarizing IC tail currents reversed at -73 +/- 5 mV in 3 mM-K solution. The reversal potential became about 30 mV more positive on raising [K]o to 15 mM. No clear change in current amplitude or tail-current reversal potential occurred on adding Cs (2 mM), reducing [Cl]o from 128 to 10 mM, or replacing external Na with Tris. The underlying conductance GC was activated at membrane potentials positive to -45 mV. At -32 mV GC showed an approximately exponential increase with time, with a time constant of approximately 0.6 sec at 26 degrees C. Repolarizing tail currents declined exponentially with time, the time constant becoming shorter with increasing negative post-pulse potentials. When the clamp was switched off at the end of a depolarizing command of sufficient amplitude and duration to activate IC, a membrane hyperpolarization to -73 mV ensued, of similar amplitude and decay time to that following spontaneous action potentials. It is concluded that the clamp current observed in these experiments is probably the Ca-activated K current thought to contribute to the post-activation after-hyperpolarization in hippocampal neurones.

Action Potentials↗
PubMed1983

Persistent slow inward calcium current in voltage-clamped hippocampal neurones of the guinea-pig.

CA1 and CA3 neurones in transverse slices of guinea-pig hippocampus were voltage clamped through a single micro-electrode, and perfused with Krebs solution containing 0.5 microM-tetrodotoxin and 10 mM-tetraethylammonium at (normally) 24-26 degrees C. Slow inward currents of less than or equal to 0.5 nA were recorded during depolarizing voltage commands to membrane potentials positive to between -40 and -30 mV. These currents peaked at 100-300 msec after the onset of the depolarizing command, then subsequently declined during continuing depolarization. This decline could be ascribed to a developing outward current since repolarizing inward current tails showed no diminution up to 700 msec. No clear evidence for time-dependent inactivation of the inward current could be obtained. A persistent component of inward current could be detected when the membrane potential was maintained above the inward current threshold, such that small hyperpolarizing commands induced an outward relaxation and large hyperpolarizations produced an inward tail current. The inward current was depressed by removing external Ca, or by adding 0.2-0.5 mM-Cd, or 0.1 mM-verapamil, and was increased by adding 1 mM-Ba. A possible role for this persistent inward current in generating the slow membrane depolarization underlying burst discharges in these neurones is discussed. In some neurones (primarily CA1), an additional fast spike-like current was recorded, which was blocked by Cd or Mn and depressed by a depolarizing pre-pulse. It is suggested that this was a manifestation of the previously-reported dendritic Ca spike.

Action Potentials↗
PubMed1982

Cholinergic transmission in cat parasympathetic ganglia.

1. Intracellular electrical recording techniques were used to study the ionic mechanisms of cholinergic synaptic transmission in cat vesical pelvic ganglia (v.p.g.). 2. Orthodromic nerve stimulation as well as ionophoretic application of acetylcholine (ACh) resulted in, first, a fast excitatory post-synaptic potential (f.e.p.s.p.) and secondly, a slow inhibitory post-synaptic potential (s.i.p.s.p). These distinct post-synaptic responses were direct actions of ACh and not mediated through an interneurone. In addition, a slow excitatory post-synaptic potential (s.e.p.s.p.) was observed in 44% of the cells. 3. The f.e.p.s.p., mediated via nicotinic receptors, had a reversal potential of -10 mV and resembled the conventional rapid depolarization in other ganglia. The s.i.p.s.p., mediated by muscarinic receptors, had a reversal potential of about -100 mV and resulted from an increase in potassium conductance. 4. The slow muscarinic hyperpolarization could be observed in the absence of antagonists and it was elicited at stimulus frequencies in the physiological range (2-10 Hz). the s.i.p.s.p. induced orthodromically or ionophoretically inhibited firing in spontaneously active neurones. These observations suggest that the muscarinic hyperpolarization may occur under physiological conditions and has sufficient magnitude to be inhibitory to neuronal activity.

Acetylcholine↗
PubMed1981

Sucrose-gap recordings of nerve-evoked potentials in mammalian parasympathetic ganglia.

The sucrose-gap recording technique was used to study mammalian parasympathetic ganglionic transmission. Both a fast nicotinic depolarization potential and a slow muscarinic hyperpolarizing potential were recorded in vesical pelvic ganglia (VPG). A long afterhyperpolarization caused by an electrical response of through-fibers was also recorded. However, a slow excitatory postsynaptic potential (S-EPSP) was not readily observed and may be masked by the long afterhyperpolarization. In addition, the slow inhibitory postsynaptic potential (S-IPSP) of the VPG was due to a direct effect of acetylcholine (ACh). Thus, sucrose-gap recordings of VPG potentials are similar to those obtained in sympathetic ganglia, but the mechanism for transmission of the S-IPSP may be different in the respective ganglia.

Acetylcholine↗
PubMed1980

An intracellular investigation of cat vesical pelvic ganglia.

1. Intracellular recording techniques were used to study individual neurons in the cat parasympathetic vesical pelvic ganglion (VPG). 2. Active and passive electrical properties were determined from 140 ganglion cells (35 preparations). 3. Three types of ganglion cells were distinguished. Type I (A and B) cells were nonaccommodating cells in response to depolarizing current pulses. Type II cells showed accommodation to depolarizing current pulses. Other cells, presumably glia, were also impaled. 4. Type IB cells exhibited two kinds of nonsynaptic spontaneous activity, spontaneous action potentials (60-70 mV) and small spontaneous potentials (up to 5 mV). Characteristics of the spontaneous activity were examined. 5. The duration of the spikes' afterhyperpolarization resulting from either orthodromic or antidromic train stimulation was dependent on the frequency of train stimulation. No long-lasting posttrain hyperpolarization was observed. 6. Chlorisondamine (10(-6) M), d-tubocurarine (10(-5) M), and hexamethonium (10(-5) M) reversibly blocked orthodromic responses. 7. The VPG is a useful model to study parasympathetic ganglionic transmission at the cellular level.

Animals↗