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PubMed2002

Disruption of coherent oscillations in inhibitory networks with anesthetics: role of GABA(A) receptor desensitization.

The effect of anesthetic drugs at central synapses can be described quantitatively by developing kinetic models of ligand-gated ion channels. Experiments have shown that the hypnotic propofol and the sedative benzodiazepine midazolam have similar effects on single inhibitory postsynaptic potentials (IPSPs) but very different effects on slow desensitization that are not revealed by examining single responses. Synchronous oscillatory activity in networks of interneurons connected by inhibitory synapses has been implicated in many hippocampal functions, and differences in the kinetics of the GABAergic response observed with anesthetics can affect this activity. Thus we have examined the effect of propofol and midazolam-enhanced IPSPs using mathematical models of self-inhibited one- and two-cell inhibitory networks. A detailed kinetic model of the GABA(A) channel incorporating receptor desensitization is used at synapses in our models. The most dramatic effect of propofol is the modulation of slow desensitization. This is only revealed when the network is driven at frequencies that are thought to be relevant to cognitive tasks performed in the hippocampus. The level of desensitization at synapses with propofol is significantly reduced compared to control synapses. In contrast, midazolam increases macroscopic desensitization at network synapses by altering receptor affinity without concurrently modifying desensitization rates. These differences in gating between the two drugs are shown to alter network activity in stereotypically different ways. Specifically, propofol dramatically increases the amount of excitatory drive necessary for synchronized behavior relative to control, which is not the case for midazolam. Moreover, the range of parameters for which synchrony occurs is larger for propofol but smaller for midazolam, relative to control. This is an important first step in linking alterations in channel kinetics with behavioral changes.

Algorithms↗
PubMed1995

The neuroactive steroid 5 alpha-tetrahydrodeoxycorticosterone increases GABAergic postsynaptic inhibition in rat neocortical neurons in vitro.

The neuroactive steroid 5 alpha-pregnane-3 alpha, 21-diol-20-one (5 alpha-tetrahydrodeoxycorticosterone; 5 alpha-THDOC) has been shown to potentiate GABA-induced chloride currents in cell cultures and subcellular preparations. In this study, we recorded from pyramidal neurons in an in vitro slice preparation of the adult rat frontal neocortex using intracellular microelectrodes. 5 alpha-THDOC (10 microM) increased and prolonged the inhibitory postsynaptic potential (IPSP). The mean maximal synaptic conductance of the early, GABAA receptor-mediated, IPSP was enhanced to more than 700%, the one at the maximum of the late, partially GABAB receptor-mediated, IPSP to approximately 400%. The progesterone/glucocorticoid receptor antagonist RU 38486 did not prevent the IPSP increase. At a concentration of 1 microM 5 alpha-THDOC increased only the early IPSP to about 125%. Responses to the iontophoretically applied specific GABAA receptor agonist muscimol but not to the specific GABAB receptor agonist L-baclofen were enhanced by 5 alpha-THDOC (10 microM). In the giga-seal whole-cell configuration when the GABAB receptor-mediated IPSP component was absent due to intracellular perfusion, 5 alpha-THDOC (10 microM) increased IPSPs to a similar extent as in the conventional microelectrode recordings. Excitatory postsynaptic potentials, resting membrane potential, input resistance and action potential amplitude were not affected by 5 alpha-THDOC (10 microM). These data demonstrate that in neocortical tissue of the rat 5 alpha-THDOC enhances GABAergic inhibition by interacting with postsynaptic GABAA receptors while synaptic excitation and parameters of electric excitability remain unchanged.

Animals↗
PubMed1989

5-HT-mediated synaptic potentials in the dorsal raphe nucleus: interactions with excitatory amino acid and GABA neurotransmission.

1. Intracellular recordings from neurons within dorsal raphe nucleus in slices from rat brain were used to study an inhibitory postsynaptic potential (IPSP) evoked by electrical stimulation. 2. The IPSP was observed in approximately 70% of neurons, had a latency to onset of 40-65 ms, reached a peak in 350-400 ms, had a total duration of 1-2 s, and reversed polarity at the potassium equilibrium potential. 3. This IPSP was blocked by spiperone (1 microM) and prolonged by fluoxetine (300 nM-30 microM) suggesting that it was mediated by 5-hydroxytryptamine (5-HT). 4. Superfusion with gamma-aminobutyric acid (GABA) and excitatory amino acid receptor antagonists were used to block "fast" synaptic potentials that preceded the IPSP such that it could be studied in isolation. Blockade of the GABA-mediated synaptic potentials increased the amplitude of the IPSP by 1.3-fold. The amplitude of the IPSP was reduced by 30% after blockade of the excitatory amino acid-mediated synaptic potential. 5. The results indicate that the IPSP recorded in dorsal raphe neurons was caused by 5-HT released at least in part from indirect (synaptically induced) excitation of 5-HT-containing cells within the slice.

Animals↗
PubMed2001

GABA(A)-dependent chloride influx modulates reversal potential of GABA(B)-mediated IPSPs in hippocampal pyramidal cells.

Changes in intracellular chloride concentration, mediated by chloride influx through GABA(A) receptor-gated channels, may modulate GABA(B) receptor-mediated inhibitory postsynaptic potentials (GABA(B) IPSPs) via unknown mechanisms. Recording from CA3 pyramidal cells in hippocampal slices, we investigated the impact of chloride influx during GABA(A) receptor-mediated IPSPs (GABA(A) IPSPs) on the properties of GABA(B) IPSPs. At relatively positive membrane potentials (near -55 mV), mossy fiber--evoked GABA(B) IPSPs were reduced (compared with their magnitude at -60 mV) when preceded by GABA(A) receptor--mediated chloride influx. This effect was not associated with a correlated reduction in membrane permeability during the GABA(B) IPSP. The mossy fiber--evoked GABA(B) IPSP showed a positive shift in reversal potential (from -99 to -93 mV) when it was preceded by a GABA(A) IPSP evoked at cell membrane potential of -55 mV as compared with -60 mV. Similarly, when intracellular chloride concentration was raised via chloride diffusion from an intracellular microelectrode, there was a reduction of the pharmacologically isolated monosynaptic GABA(B) IPSP and a concurrent shift of GABA(B) IPSP reversal potential from -98 to -90 mV. We conclude that in hippocampal pyramidal cells, in which "resting" membrane potential is near action potential threshold, chloride influx via GABA(A) IPSPs shifts the reversal potential of subsequent GABA(B) receptor--mediated postsynaptic responses in a positive direction and reduces their magnitude.

2-Amino-5-phosphonovalerate↗
PubMed1989

EPSPs in rat neocortical neurons in vitro. I. Electrophysiological evidence for two distinct EPSPs.

1. To investigate excitatory postsynaptic potentials (EPSPs), intracellular recordings were performed in layer II/III neurons of the rat medial frontal cortex. The average resting membrane potential of the neurons was more than -75 mV and their average input resistance was greater than 20 M omega. The amplitudes of the action potentials evoked by injection of depolarizing current pulses were greater than 100 mV. The electrophysiological properties of the neurons recorded were similar to those of regular-spiking pyramidal cells. 2. Current-voltage relationships, determined by injecting inward and outward current pulses, displayed considerable inward rectification in both the depolarizing and hyperpolarizing directions. The steady-state input resistance increased with depolarization and decreased with hyperpolarization, concomitant with increases and decreases, respectively, in the membrane time constant. 3. Postsynaptic potentials were evoked by electrical stimulation via a bipolar electrode positioned in layer IV of the neocortex. Stimulus-response relationships, determined by gradually increasing the stimulus intensity, were consistent among the population of neurons examined. A short-latency EPSP [early EPSP (eEPSP)] was the response with the lowest threshold. Amplitudes of the eEPSP ranged from 4 to 8 mV. Following a hyperpolarization of the membrane potential, the amplitude of the eEPSP decreased. Upon depolarization, a slight increase in amplitude and duration was observed, accompanied by a significant increase in time to peak. 4. The membrane current underlying the eEPSP (eEPSC) was measured using the single-electrode voltage-clamp method. The amplitude of the eEPSC was apparently independent of the membrane potential in 8 of 12 neurons tested. In the other 4 neurons, the amplitude of the eEPSC increased with hyperpolarization and decreased with depolarization. 5. Higher stimulus intensities evoked, in addition to the eEPSP, a delayed EPSP [late EPSP (lEPSP)] in greater than 90% of the neurons tested. The amplitude of the lEPSP ranged from 12 to 20 mV, and the latency varied between 20 and 60 ms. The amplitude of the lEPSP varied with membrane potential, decreasing with depolarization and increasing following hyperpolarization. The membrane current underlying the lEPSP (lEPSC) displayed a similar voltage dependence. 6. At stimulus intensities that led to the activation of inhibitory postsynaptic potentials (IPSPs), the lEPSP was no longer observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Variation in strength of inhibitory synapses in the CA3 region of guinea-pig hippocampus in vitro.

1. Simultaneous recordings were made from inhibitory cells located close to the stratum pyramidale and from pyramidal cells in the CA3 region of guinea-pig hippocampal slices, to examine inhibitory synaptic interactions. 2. The average amplitude of inhibitory postsynaptic potentials (IPSPs) initiated by single action potentials at different synapses varied between 0.3 and 2.6 mV. Experiments were performed to investigate the source of this variation. 3. Unitary IPSPs reversed at similar potentials to the first phase of the synaptic inhibition elicited by afferent fibre stimulation. IPSPs evoked by single action potentials or repetitive inhibitory cell firing were suppressed by picrotoxin, a gamma-aminobutyric acid (GABAA) receptor antagonists. 4. The time to peak and amplitude of averaged IPSPs were not related as predicted if amplitude variations resulted simply from different electrotonic locations of inhibitory terminals. 5. Transmission failures could be resolved at connections which generated small averaged IPSPs, but were not apparent at connections where averaged IPSPs were large. 6. IPSPs elicited by the same inhibitory cell in several pyramidal cells were of similar amplitude. The amplitudes of simultaneous IPSPs impinging on pairs of neighboring pyramidal cells were positively correlated. 7. Thus, the variation in efficacy of inhibitory synapses may result from differences in transmitter release from different inhibitory cells and not from postsynaptic factors.

2-Amino-5-phosphonovalerate↗
PubMed1990

Recurrent inhibition to and from motoneurons innervating the flexor digitorum and flexor hallucis longus muscles of the cat.

1. Recurrent inhibitory postsynaptic potentials (IPSPs) to and from motoneurons innervating the flexor digitorum longus (FDL) and flexor hallucis longus (FHL) muscles of the cat were investigated to determine whether recurrent inhibitory projections involving these motoneurons are similar--as would be consistent with the Ia and anatomic synergism of FDL and FHL--or are dissimilar, as are the activities of these muscles during locomotion (O'Donovan et al. 1982). 2. Composite recurrent IPSPs were recorded in several species of motoneurons innervating hindlimb muscles in response to stimulation of a number of muscle nerves in cats allowed to become unanesthetized after ischemic decapitation. 3. No recurrent IPSPs from stimulation of the FDL nerve were observed in motoneurons innervating FDL, FHL, lateral gastrocnemius-soleus (LG-S), medial gastrocnemius (MG), plantaris (Pl), tibialis anterior (TA), or extensor digitorum longus (EDL). 4. The recurrent IPSPs produced by stimulation of FHL were larger and found more frequently in LG-S than in FDL motoneurons. Recurrent inhibition from FHL was also greater in Pl than in FDL motoneurons. 5. The recurrent IPSPs produced by stimulation of LG-S, PL, and MG were larger in FHL than in FDL motoneurons, and those from LG-S and MG were found more frequently in FHL than in FDL motoneurons. 6. Stimulation of the TA nerve produces recurrent IPSPs in FDL but not in FHL motoneurons. A few FDL and FHL cells (6 of 23 and 9 of 34, respectively) received small (less than 0.5 mV) recurrent IPSPs from stimulation of the EDL nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Direct evidence for recurrent inhibition in sliced brain preparation of the cat's visual cortex.

To reveal the recurrent inhibitory circuit in the visual cortex, a depolarizing current was applied through a glass microelectrode to an impaled cell in an in vitro slice of the visual cortex obtained from a cat anesthetized with pentobarbital. The cell reported here produced inhibitory postsynaptic potentials (IPSPs) following single spikes or bursts of spikes which were elicited by intracellularly applied current. This observation indicates that IPSPs have been mediated by the recurrent inhibitory circuit via axon collaterals of the impaled cell.

Action Potentials↗
PubMed1995

Role of the ferret perigeniculate nucleus in the generation of synchronized oscillations in vitro.

1. The cellular mechanisms by which neurons of the ferret perigeniculate nucleus (PGN) participate in the generation of spindle waves and slowed absence seizure-like oscillations were investigated with intracellular and extracellular recording techniques in geniculate slices maintained in vitro. 2. During spindle wave generation, PGN neurons generated repetitive (2-9 Hz) high frequency (up to 500 Hz) burst discharges mediated by the activation of a low threshold Ca2+ spike by the arrival of barrages of excitatory postsynaptic potentials (EPSPs). In most PGN cells at resting membrane potentials (-60 to -70 mV) spindle waves were associated with a progressive hyperpolarization that persisted as a prolonged after-hyperpolarization. 3. The EPSPs occurring in PGN cells were highly synchronized with burst firing in the neighbouring portion of the dorsal lateral geniculate nucleus (LGNd) and were intermixed with short duration inhibitory postsynaptic potentials (IPSPs). After block of GABAergic receptors, the EPSPs occurring during the generation of spindle waves reversed polarity at around 0 mV. In addition, these EPSPs were completely blocked with the bath application of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), as was spindle wave generation in both the PGN and LGNd. 4. Slowing the intraspindle frequency to 2-4 Hz with pharmacological block of GABAA receptors resulted in a marked increase in the intensity of burst firing by PGN cells such that the number of action potentials per burst increased from a maximum of thirteen to a maximum of sixty. Block of GABAA receptors also resulted in a marked increase in the amplitude and duration of the EPSP barrages arriving from the relay laminae during generation of the slowed oscillation. 5. These findings indicate that spindle waves are generated in the ferret LGNd in vitro through an interaction between the GABAergic neurons of the PGN and relay neurons, such that burst firing in relay neurons activates a barrage of EPSPs and a subsequent low threshold Ca2+ spike in PGN cells. This activation of PGN neurons inhibits a substantial number of relay cells, a few of which rebound burst after this IPSP, thus starting the cycle again. Block of GABAA receptors results in a marked enhancement of activity in PGN cells through increased excitation from relay cells and disinhibition from neighbouring PGN cells. This increased activity in PGN neurons results in a markedly enhanced activation of GABAB receptors in relay neurons and the subsequent generation of paroxysmal activity that is similar to that associated with absence seizures.

Animals↗
PubMed2001

Excitatory synaptic inputs on myenteric Dogiel type II neurones of the pig ileum.

The synaptic input on myenteric Dogiel type II neurones (n = 63) obtained from the ileum of 17 pigs was studied by intracellular recording. In 77% of the neurones, electrical stimulation of a fibre tract evoked fast excitatory postsynaptic potentials (fEPSPs) with an amplitude of 6 +/- 5 mV (mean +/- S.D.) and lasting 49 +/- 29 ms. The nicotinic nature of the fEPSPs was demonstrated by superfusing hexamethonium (20 microM). High-frequency stimulation (up to 20 Hz, 3 seconds) did not result in a rundown of the fEPSPs, and did not evoke slow excitatory or inhibitory postsynaptic potentials. The effects of neurotransmitters, possibly involved in these excitatory responses, were investigated. Pressure microejection of acetylcholine (10 mM in pipette) resulted in a fast nicotinic depolarisation in 67%(18/27) of the neurones (13 +/- 9 mV, duration 7.0 +/- 7.2 seconds) as did 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) application (10 mM; 14 +/- 10 mV, duration 4.1 +/- 2.8 seconds) in 76% of the cells. The fast nicotinic response to acetylcholine was sometimes (6/27) followed by a slow muscarinic depolarisation (8 +/- 4 mV; duration 38.7 +/- 10.8 seconds). Immunostaining revealed 5-hydroxytryptamine hydrochloride (5-HT)- and calcitonin gene-related peptide (CGRP)-positive neuronal baskets distributed around and in close vicinity to Dogiel type II neuronal cell bodies. Microejection of 5-HT (10 mM) resulted in a fast nicotinic-like depolarisation (12 +/- 6 mV, duration 3.0 +/- 1.3 seconds) in 4 of 8 neurones tested, whereas microejection of CGRP (20 mM) gave rise to a slow muscarinic-like depolarisation (6 +/- 2 mV, duration 56.0 +/- 27.5 seconds) in 8 of 12 neurones tested. In conclusion, myenteric Dogiel type II neurones in the porcine ileum receive diverse synaptic input. Mainly with regard to the prominent presence of nicotinic responses, these neurones behave contrary to their guinea pig counterparts.

Acetylcholine↗
PubMed2004

The unique inhibitory potentials in motoneurons that occur during active sleep are comprised of minimal unitary potentials.

Loss of muscle tone during active (rapid-eye-movement, REM) sleep is due to the inhibition of motoneurons. This inhibition is manifest in high-gain intracellular electrophysiological records as hyperpolarizing synaptic noise, which includes large amplitude active sleep-specific inhibitory postsynaptic potentials (IPSPs). We report here evidence that the large active sleep-specific IPSPs are comprised of a small number of minimal unitary potentials that are characterized by fast rise-times (10-90% rise-times < or = 0.75 ms); they are present in high-gain records during quiet sleep or during active sleep where they are intermingled with larger active sleep-specific IPSPs with 10-90% rise-times > or = 1.00 ms and amplitudes that are integer multiples of the minimal unitary potentials. In hypoglossal motoneurons, the amplitude of these minimal unitary potentials averaged 0.33 +/- 0.04 mV (mean +/- S.D., n = 6). It is concluded that the large IPSPs with slow rise-times that are observed in motoneurons during active sleep are due to the nearly simultaneous arrival of multiple (< or = 5) minimal unitary potentials. We hypothesize that the same inhibitory interneurons that produce small IPSPs with fast rise-times during quiet sleep are also responsible for the large amplitude active sleep-specific IPSPs.

Afferent Pathways↗
PubMed2003

Modulatory inputs on sympathetic neurons in the rostral ventrolateral medulla in the rat.

1. The first part of this study looks at spontaneously active neurons located in the rostral ventrolateral medulla (RVLM) with projections to the thoracic spinal cord. Sixteen neurons were intracellularly recorded in vivo. Four out of 16 neurons were antidromically activated from the thoracic spinal cord (axonal conduction velocities varied from 1.8 m/s to 9.5 m/s). 2. The simultaneous averages of the neuronal membrane potential and arterial blood pressure triggered by the pulsatile arterial wave or the EKG-R wave demonstrated changes in membrane potential (hyperpolarization or depolarization) locked to the cardiac cycle in four neurons in this group. These neurons (three of them bulbospinal) were further tested for barosensitivity by characterizing the responses to electrical stimulation of the aortic depressor nerve. Four neurons responded with inhibitory hyperpolarizing responses characterized as inhibitory postsynaptic potentials (IPSP) to aortic nerve stimulation (onset latency: 32.3 +/- 5.0 ms; mean +/- SEM). 3. In two neurons in the RVLM, one of them characterized as barosensitive, electrical stimulation of the opposite RVLM (0.5 Hz, 1.0 ms pulse duration, 25-100 microA) elicited excitatory postsynaptic potentials (EPSPs) with latencies of 9.07 and 10.5 ms. At resting membrane potential, the onset latency of the evoked EPSPs did not change with increasing stimulus intensities. Some of the recorded neurons were intracellularly labelled with biocytin for visualization. They were found in the RVLM. 4. These experiments in vivo would support the idea of a functional commissural pathway between the RVLM of both sides. 5. Anatomical data have shown that some of those commissural bundle fibers originate in the C1 adrenergic neuronal group in the RVLM. In the second part of this study, we used an intracellular recording technique in vitro to investigate the effects of the indirect adrenergic agonist tyramine on neurons in the RVLM with electrophysiological properties similar to premotor sympathetic neurons in vivo. 6. Tyramine (0.5-1 mM) produced a pronounced inhibitory effect with hyperpolarization and increase in membrane input resistance on two neurons characterized as regularly firing (R), and on one neuron characterized as irregularly firing (1). This effect was preceded by a transient depolarization with increases in firing rate. 7. These results would indicate that neurons in the RVLM recorded in vitro and with properties similar to premotor sympathetic neurons can be modulated by catecholamines released from terminals probably making synaptic contacts.

Action Potentials↗
PubMed2004

Odor-evoked responses in the olfactory center neurons in the terrestrial slug.

The procerebrum (PC) of the terrestrial mollusk Limax is a highly developed second-order olfactory center consisting of two electrophysiologically distinct populations of neurons: nonbursting (NB) and bursting (B). NB neurons are by far the more numerous of the two cell types. They receive direct synaptic inputs from afferent fibers from the tentacle ganglion, the primary olfactory center, and also receive periodic inhibitory postsynaptic potentials (IPSPs) from B neurons. Odor-evoked activity in the NB neurons was examined using perforated patch recordings. Stimulation of the superior tentacle with odorants resulted in inhibitory responses in 45% of NB neurons, while 11% of NB neurons showed an excitatory response. The specific response was reproducible in each neuron to the same odorant, suggesting the possibility that activity of NB neurons may encode odor identity. Analysis of the cycle-averaged membrane potential of NB neurons revealed a correlation between the firing rate and the membrane potential at the plateau phase between IPSPs. Also, the firing rate of NB neurons was affected by the frequency of the IPSPs. These results indicate the existence of two distinct mechanisms for the regulation of NB neuron activity.

Action Potentials↗
PubMed1991

Osmotic effects on the CA1 neuronal population in hippocampal slices with special reference to glucose.

1. Lowered osmolality promotes epileptiform activity both clinically and in the hippocampal slice preparation, but it is unclear how neurons are excited. We studied the effects of altered osmolality on the electrophysiological properties of CA1 pyramidal cells in hippocampal slices by the use of field and intracellular recordings. The excitability of these neurons under various osmotic conditions was gauged by population spike (PS) amplitude, single cell properties, and evoked synaptic input. 2. The orthodromic PS recorded in stratum pyramidale and the field excitatory postsynaptic potential (EPSP) in stratum radiatum were inversely proportional in amplitude to the artificial cerebrospinal fluid (ACSF) osmolality over a range of +/- 80 milliosmoles/kgH2O (mosM). The effect was osmotic because changes occurred within the time frame expected for cellular expansion or shrinkage and because permeable substances such as dimethyl sulfoxide or glycerol were without effect. Dilutional changes in ACSF constituents were experimentally ruled out as promoting excitability. 3. To test whether the field data resulted from a change in single-cell excitability, CA1 cells were intracellularly recorded during exposure to +/- 40 mosM ACSF over 15 min. There was no consistent effect upon CA1 resting potential, cell input resistance, or action potential threshold. 4. Osmotic alteration of orthodromic and antidromic field potentials might involve a change in axonal excitability. However, the evoked afferent volley recorded in CA1 stratum pyramidale or radiatum, which represents the compound action potential (CAP) generated in presynaptic axons, remained osmotically unresponsive with regard to amplitude, duration, or latency. This was also characteristic of CAPs evoked in isolated sciatic and vagus nerve preparations exposed to +/- 80 mosM. Therefore axonal excitability and associated extracellular current flow generated periaxonally are not significantly affected by osmotic shifts. 5. The osmotic effect on field potential amplitudes appeared to be independent of synaptic transmission because the inverse relationship with osmolality held for the antidromically evoked PS. Moreover, as recorded with respect to ground, the intracellular EPSP-inhibitory postsynaptic potential (IPSP) sequence (evoked from CA3 stratum radiatum) was not altered by osmolality. 6. The PS could occasionally be recorded intracellularly as a brief negativity interrupting the evoked EPSP. In hyposmotic ACSF, the amplitude increased and action potentials arose from the trough of the negativity as expected for a field effect. This is presumably the result of enhanced intracellular channeling of current caused by the increased extracellular resistance that accompanies cellular swelling.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1985

Effects of cholecystokinin, caerulein and pentagastrin on electrical behavior of myenteric neurons.

Intracellular methods were used to record the electrical behavior of myenteric neurons from guinea-pig ileum in vitro. Cholecystokinin-octapeptide (CCK-8) at 1 to 100 microM in the ejection pipettes were applied to the neurons by pressure microejection. CCK-8 (0.01 to 1 microM) and caerulein (0.01 to 0.1 microM) were applied also in the superfusion solution. CCK-8, applied by either method, evoked a long-lasting depolarization of the cell membranes that was associated with an increase in the input resistance, suppression of hyperpolarizing afterpotentials and enhanced excitability. The enhanced excitability was reflected by increased probability of action potential discharge during membrane depolarization by intracellularly injected current. Caerulein evoked the same excitatory responses as CCK-8. The actions of both agents simulated slow synaptic excitation in the neurons. In another group of AH/type 2 neurons, CCK-8 evoked a long-lasting membrane hyperpolarization and decreased input resistance that mimicked stimulus-evoked slow inhibitory postsynaptic potentials. Hyperpolarizing responses were never evoked by caerulein. About 25% of tested neurons failed to respond to CCK-8 and 70% did not respond to caerulein. Pentagastrin (1 microM in the superfusion solution) did not affect the electrical behavior of the neurons. The results are consistent with a neurotransmitter role for cholecystokinin that could be either excitatory of inhibitory in the enteric nervous system.

Animals↗
PubMed1998

Frequency-dependent inhibition of neuronal activity by topiramate in rat hippocampal slices.

1. Topiramate is a structurally novel anticonvulsant which was recently approved for adjunctive therapy in partial and secondarily generalized seizures. The present study was aimed at elucidating the mechanisms underlying the anticonvulsant efficacy of topiramate using intra- and extracellular recording techniques in the in vitro hippocampal slices. 2. When stimuli were delivered every 20 s, topiramate had no measurable effect on both field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs). However, increasing the stimulation frequency from 0.05-0.2 Hz, topiramate significantly decreased the slope of fEPSP and the amplitude of PS in a concentration-dependent manner. The amplitude of presynaptic fiber volley was also reduced. 3. Topiramate did not affect the magnitude of paired-pulse inhibition and monosynaptically evoked inhibitory postsynaptic potentials (IPSPs). 4. Sustained repetitive firing was elicited by injection of long duration (500 ms) depolarizing current pulses (500-800 pA). Superfusion with topiramate significantly reduced the number of action potentials evoked by a given current pulse. 5. After blockade of GABA receptors by bicuculline, burst firing which consisted of a train of several spikes riding on a large depolarizing wave termed paroxysmal depolarizing shift (PDS) was recorded. Application of topiramate reduced the duration of PDS and later spikes with less effect on the initial action potential. 6. These results suggest that frequency-dependent inhibition of neuronal activity due to blockade of Na+ channels may account largely for the anticonvulsant efficacy of topiramate.

Action Potentials↗
PubMed1984

Synaptic transmission from muscle afferents during fictive locomotion in the mesencephalic cat.

Modulation of synaptic potentials produced by electrical stimulation of low-threshold muscle afferents in lumbar alpha-motoneurons innervating knee and ankle muscles was studied by intracellular recording during "fictive locomotion" induced by stimulating the mesencephalic locomotor region (MLR) in paralyzed, mesencephalic cats. Averaging postsynaptic potentials in different phases of the fictive step cycle indicated that relatively little amplitude modulation occurred. In nearly half of the 38 motoneurons analyzed, there was a statistically significant tendency for excitatory postsynaptic potentials (EPSPs) to increase in amplitude during the depolarized phase of the oscillation in the membrane potential produced during fictive locomotion (locomotor-drive potential). In 8% the EPSPs decreased under the same conditions, while the rest displayed a constant amplitude during all phases of the fictive step cycle. Only three cells showed a distinct second peak in the EPSP at a latency consistent with transmission in a di- or trisynaptic pathway. Late inhibitory postsynaptic potentials (IPSPs) were also rarely observed. Thus oligosynaptic pathways from muscle afferents to the motoneuron groups studied are not prominent during the locomotor cycle in this preparation. We suggest that the marked modulation of monosynaptic reflex amplitude observed in mesencephalic cats (1) arises mainly from the effects of the locomotor-drive potential in bringing the cells closer to threshold during some phases of locomotion. Specific modulation during fictive locomotion of transmission in pathways from muscle afferents, which has been demonstrated for cutaneous pathways (28), was not observed. The implications of these results for the control of locomotion are discussed briefly.

Animals↗