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An intracellular analysis of dendrodendritic inhibition in the turtle in vitro olfactory bulb.

1. Intracellular recordings from an in vitro preparation of turtle olfactory bulb were used to determine the pathway responsible for producing synaptic inhibition of mitral cells.2. Inhibitory post-synaptic potentials (i.p.s.p.s) could be elicited in mitral cells by both olfactory nerve (orthodromic) and mitral cell axon (antidromic) stimulation and by suprathreshold depolarizing current pulses injected intracellularly through the recording micro-electrode. Reversing the chloride gradient by either intracellular injection of chloride or lowering the external chloride concentration reversed the i.p.s.p.s into depolarizing potentials. The GABA antagonists, bicuculline and picrotoxin, blocked the i.p.s.p.s.3. A large increment in the size of the orthodromic and antidromic i.p.s.p. was associated with an action potential. Grading the stimulus intensity on either side of threshold resulted in graded changes in the size of the i.p.s.p. The increment associated with an action potential and the ability to evoke an i.p.s.p. by direct stimulation of a mitral cell suggested that these phenomena were due to activation of the dendrodendritic reciprocal synapses between mitral and granule cells.4. Orthodromic, antidromic and directly produced action potentials could be fractionated such that regenerative activation of the soma-dendritic membrane could be blocked. Only when this membrane was allowed to reach threshold was a large i.p.s.p. recorded. This indicated that the increment in the i.p.s.p. was due to activation of a synaptic pathway involving the soma-dendritic membrane.5. When spike propagation in the mitral cell axons was blocked by tetrodotoxin (TTX), an i.p.s.p. could still be produced by direct stimulation, indicating that the mitral cell soma-dendritic membrane is functionally both pre- and post-synaptic. TTX blocked the fast, high amplitude somatic spikes and revealed higher threshold, broader spikes of lower amplitude that were blocked by cobalt and calcium-free Ringer.6. Tetraethylammonium (TEA) increased the duration and the amplitude of the calcium spike. The amplitude was also increased by barium which prolonged the spike only if TEA was present. In the presence of TEA, bicuculline also prolonged the calcium spike. This suggests that three ionic conductances limit the duration of the calcium action potential: a voltage-dependent potassium conductance, a calcium-dependent potassium conductance, and the chloride conductance associated with the i.p.s.p.7. Spontaneous, bicuculline-sensitive, depolarizing potentials were recorded in mitral cells impaled with KCl-filled electrodes. Orthodromic or antidromic stimulation increased the frequency of these small potentials for the duration of the i.p.s.p., indicating prolonged GABA release.8. Stimulation of the olfactory nerves, the mitral cell axons, and direct stimulation could elicit action potentials in granule layer cells. Orthodromic and antidromic activation was followed by a hyperpolarization of about the same duration as the mitral cell i.p.s.p. and was probably the result of dysfacilitation.9. Paired stimulation of the mitral cell axons resulted in the diminution of the granule cell e.p.s.p. evoked by the second shock, indicating that the predominant excitatory input to the granule cells is through the mitral cell dendrites.10. It is concluded that both synaptic inhibition of mitral cells and excitation of granule cells is mediated primarily by the dendrodendritic reciprocal pathway.

Action Potentials↗

Electrophysiological characterization of laminar synaptic inputs to the olfactory tubercle of the rat studied in vitro: modulation of glutamatergic transmission by cholinergic agents is pathway-specific.

We have exploited the complementary arrangement of afferents in a coronal slice (300-400 microm) of the rat olfactory tubercle (OT) maintained in vitro to investigate transmission in two separate synaptic pathways. We recorded extracellular responses within the OT dense cell layer in slices and stimulated either the outermost layer to activate primary olfactory fibres or deeper to activate secondary input. Superficial stimulation produced a synaptic potential with superimposed population spike. This interpretation was based on blockade by calcium removal from the bathing medium and the use of the glutamate antagonist DNQX (10 microM); the spike was found to be selectively suppressed by tetrodotoxin applied near the cells. The spike, but not the synaptic wave, was depressed by 12 mM Ca2+ and enhanced by 1 mM Ba2+ in the bathing medium. Deep stimulation to activate association and intrinsic fibres elicited a nerve volley followed by a later response, also blocked by Ca2+ removal or 10 microM DNQX. It was unaffected by high Ca2+ or Ba2+, hence resulting from synaptic and not action current flow. Removal of Mg2+ from the bathing medium revealed an NMDA component of synaptic transmission at both loci that was selectively blocked by D-AP-5. The deep synaptic response, only, was depressed by carbachol IC50 7 microM or muscarine IC50 13 microM. This depression was also induced by AChE inhibitors eserine or tacrine and was antagonized by 1 microM atropine or 5-10 microM clozapine. These results characterize transmission in the OT and demonstrate a role for muscarinic modulation of deeper synapses in the OT that is influenced by psychotherapeutic drugs.

Animals↗

Regional differences in glial cell modulation of synaptic transmission.

Metabolic integrity of glial cells in field CA1 of the guinea pig hippocampus is critical to maintenance of synaptic transmission (Keyser and Pellmar [1994] Glia 10:237-243). To determine if this tight glial-neuronal coupling is equally important in other brain regions, we compared the effect of fluoroacetate (FAC), a glial specific metabolic blocker, on synaptic transmission in field CA1 to synaptic transmission in area dentata (DG). FAC was significantly more effective in decreasing synaptic potentials in CA1 than in DG. A similar regional disparity in the FAC-induced decrease in ATP levels was evident. Isocitrate, a glial specific metabolic substrate, prevented the FAC-induced synaptic depression in both CA1 and DG. The results suggest that glia of CA1 and dentate respond differently to metabolic challenge. Modulation of this glial-neuronal coupling could provide a regionally specific mechanism for synaptic plasticity. Additionally, site-specific glial-neuronal interactions can impact on a variety of physiological and pathophysiological conditions.

Animals↗

Active dendritic properties constrain input-output relationships in neurons of the central olfactory pathway in the crayfish forebrain.

Parasol cells are multimodal sensory interneurons of the hemi-ellipsoid body in the decapod forebrain. In reptant crustaceans, the hemi-ellipsoid body resides in the base of the eyecup, as an appendage to the terminal medulla. Parasol cells exhibit periodic depolarizations at a frequency of 0.5-1.0 Hz. I have investigated the role of these periodic depolarizations and their superimposed impulse bursts in affecting the input/output properties of these neurons. Parasol cells receive input from photic, olfactory, and mechanosensory pathways. Strong stimulation over any one of these pathways can lead to the generation of one or more impulse bursts in a subset of parasol cells, timed to occur at the peak of successive periodic depolarizations. A role for the periodic depolarizations in the function of the parasol cells has yet to be established. I suggest the possibility that they may act as a nonlinear amplifier that boosts spatially-summated excitatory synaptic potentials from strong or appropriate stimuli above threshold for burst generation. Another possibility includes modification of voltage-sensitive ion channels in the dendritic membrane, permitting a more effective spread of excitatory synaptic currents to impulse or burst initiating zones. Impulse bursts may be a highly effective mode of output for these neurons, especially so as they occur synchronously in a subset of cells in response to strong sensory input. Furthermore, backfiring of bursts into the dendritic tree has a brief (2-3 second) but effective suppressive action upon weak sensory input, which can thereby be masked by stronger, burst-generating input. This masking phenomenon is seen in other arthropod sensory interneurons, where its physiological basis appears to be a transient accumulation of intracellular Ca(++) ions that open calcium-sensitive potassium channels.

Animals↗

Electrophysiological evidence against the hypothesis that corticospinal fibres send collaterals to the lateral reticular nucleus.

Extracellular focal synaptic potentials (FSPs) were recorded in forelimb segments of cats in the region where corticospinal volleys (pyramidal stimulation) gave a maximal FSP. No FSP was recorded in this region on stimulation of the medial part of the lateral reticular nucleus (LRN), provided that ventral spinal pathways through which FSPs can be evoked from the LRN region were transected. It is postulated that the projection from the cerebral cortex to the LRN is not by collaterals from corticospinal neurones but rather by separate corticofugal neurones.

Animals↗

Spatial performance correlates with in vitro potentiation in young and aged Fischer 344 rats.

Young adult (2-4 months old) and aged (24-26 months old) Fischer 344 (F344) rats were trained for spatial behavior (locating a hidden escape platform) in a circular water maze. The aged rats showed deficits in both the acquisition and retention of the learned response. Following the behavioral training, hippocampal slices from the rats were prepared. Potentiation of CA1 extracellular, somatic field potentials was studied in vitro following either a short stimulus train (4 pulses) or a longer train (50 pulses). Slices from the aged rats showed less short-term potentiation (124.8 +/- 4.9% baseline, mean +/- S.E.M.) at 1 min following the short train in comparison to slices from the young rats (151.8 +/- 7.5%, P less than 0.05). However, following the longer train, no differences were found between the groups in the degree of either short-term (measured at 1 min after stimulation) or long-term potentiation (measured at 60 min). The amount of potentiation seen at various time points after either train correlated with the behavioral measure of retention. These results indicate that F344 rats exhibit age-related behavioral deficits, and age-related synaptic potentiation deficits in response to short stimulation trains. The correlation between the degree of potentiation (both short-term and long-term) and retention of a behavioral task adds strength to the hypothesis that potentiation mechanisms may underlie memory processes.

Aging↗

High-frequency stimulation of the basolateral amygdala facilitates the induction of long-term potentiation in the dentate gyrus in vivo.

We investigated the effect of high-frequency stimulation of the basolateral amygdala (BLA) on the induction of long-term potentiation (LTP) in the medial perforant path (PP)-dentate gyrus (DG) synapses of anesthetized rats. A conditioning stimulation (100 pulses at 100 Hz) of the ipsilateral BLA did not change the DG synaptic potential. However, when the BLA conditioning stimulation was applied at the same time as a weak tetanic stimulation of PP (20 pulses at 20 Hz) which alone did not induce LTP, robust DG LTP was induced. Simultaneous application of contralateral BLA stimulation and PP weak tetanus did not induce LTP. Moreover, the ipsilateral BLA stimulation enhanced the magnitude of LTP induced by a moderate tetanic stimulation of PP (30 pulses at 60 Hz), but did not further enhance the LTP induced by a strong tetanic stimulation of PP (100 pulses at 100 Hz). These results suggest that the ipsilateral BLA neurons modulate the induction of DG LTP in vivo.

Amygdala↗

An integrin binding peptide reduces rat CA1 hippocampal long-term potentiation during the first few minutes following theta burst stimulation.

The integrin binding peptide GRGDSP was tested on Schaffer to CA1 (Sch-CA1) long-term potentiation (LTP) in the rat hippocampal slice. Experiments in which GRGDSP was bath applied for 50 min, beginning 10 min before theta burst stimulation (TBS), reduced LTP of the field excitatory post synaptic potential in a concentration dependent manner, with 250 microM producing a significant decrease. However, LTP was not affected when 250 microM GRGDSP was applied 30 min post-TBS, nor when applied as soon as 5 min post-TBS. When 250 microM GRGDSP was applied for only 10 min pre- to 5 min post-TBS, this brief application was sufficient in reducing LTP similar to the extended 50 min application. We conclude that RGD-binding integrins involved in LTP are only momentarily responsive to peptide-mediated antagonism in the first few minutes following TBS.

Animals↗

Modulation of afferent-evoked neurotransmission by 5-HT3 receptors in young rat dorsal horn neurones in vitro: a putative mechanism of 5-HT3 induced anti-nociception.

1. The in vitro hemisected spinal cord from young rat was used to investigate the mechanism of serotoninergic modulation of primary afferent-mediated synaptic transmission in the dorsal horn through activation of the 5-HT3 receptor. 2. Dorsal root-evoked excitatory post-synaptic potentials (DR-EPSPs) were recorded intracellularly from dorsal horn neurones. Extracellular recordings of the population primary afferent depolarization (PAD) and the dorsal root-evoked dorsal root reflex (DR-DRR) were made from segmental dorsal roots. 3. 5-Hydroxytryptamine (5-HT) and the selective 5-HT3 receptor agonist 1-(m-chloro-phenyl)-biguanide hydrochloride (m-ChPB) (10 and 50 microM) induced statistically significant reductions of the DR-EPSP amplitude (P<0.001) and duration (P<0.001) in the majority of dorsal horn neurones. The 5-HT3 receptor selective antagonists 3-Tropanyl-indole-3-carboxylate hydrochloride (Tropisetron, 10 microM) and N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-chloro-4-methyl-3-oxo-3,4-dihydro-2H-1 ,4-benzoxazine-8-carboxamide (Y-25130, 10 microM) abolished m-ChPB-induced DR-EPSP attenuation and partially blocked the 5-HT effect. 4. m-ChPB (50 microM)-induced DR-EPSP amplitude and duration attenuation was retained in the presence of the GABA(A) receptor antagonist bicuculline (30 microM), the GABA(B) receptor antagonist saclofen (50 microM) and the opioid receptor antagonist naloxone (50 microM). 5. Both 5-HT and m-ChPB (10 and 50 microM) induced a PAD but the mean peak amplitude of 5-HT-induced PAD was significantly greater than PAD to m-ChPB (98.6+/-12 microV compared to 51.8+/-10 V for 50 microM of agonist, respectively). Tropisetron partially reduced 5-HT-induced PAD and abolished m-ChPB-induced PAD. 5-HT, but not m-ChPB, significantly (P<0.001) reduced the peak amplitude of the DR-DRR and this action of 5-HT was unaffected by Tropisetron or Y-25130. 6. These data provide experimental evidence for a putative cellular mechanism at the level of the dorsal horn for anti-nociceptive effects of 5-HT3 receptor activation. This 5-HT3-mediated modulation of sensory afferent transmission was evidently independent of inhibitory GABA- or opioid-dependent interneuronal pathways. The extent to which the 5-HT3 receptor could be involved in the operation of endogenous analgesia and sensory modulation by descending monoamine bulbo-spinal pathways is discussed.

Analgesia↗

A phorbol diester-induced enhancement of synaptic transmission in olfactory cortex.

1. Extracellular field synaptic potentials were recorded from pial surface slices of guinea-pig olfactory cortex maintained in vitro. 2. Phorbol 12,13-dibutyrate (0.1-10 microM) enhanced the amplitude of the evoked potential (by 51.2 +/- 10.4% with 1 microM) in normal solution. When the evoked potential was partially depressed by Cd, Co, Mn or a reduced Ca concentration, phorbol 12,13-dibutyrate (1 microM) induced a much larger enhancement of the evoked potential (196.5 +/- 24.4% increase). Phorbol 12,13-diacetate and mezerein had similar effects but were less potent. 4 beta-Phorbol (10 microM) had no effect. 3. The diacylglycerol analogues, dioctanoylglycerol (100-1000 microM), 1-oleoyl-2-acetylglycerol (100-500 microM) or diolein (100 microM) had no effect on the evoked potentials, either alone or in the presence of Cd. 4. The isoquinolinylsulphonamide inhibitor (H-7) of protein kinase C slightly enhanced the e.p.s.p. and had no effect on the potentiation produced by phorbol ester. Another protein kinase C inhibitor, acridine orange (100-1000 microM), had no effect on the action of phorbol ester. 5. These results show that transmitter release, as at other synapses, is enhanced by phorbol esters but Ca did not potentiate this action. The pharmacological profile of the effect on transmitter release differed from that of protein kinase C in cell-free preparations and therefore it is unclear whether protein kinase C was involved in the present study.

Animals↗

The influences of phenytoin on the fundamental electrical properties of simple neural systems.

The effects of phenytoin on some neurophysiological properties of simple neuronal systems are reviewed. From all the available data phenytoin decreases or has no effect on post-tetanic hyperpolarization, which is interpreted as an expression of the electrogenic pump. Although in some neurons the membrane conductance is increased, the resting membrane potential is minimally affected. The effect on the action potential varies with different preparations and with different neurons of the same ganglion. If an effect is present, the overshoot is decreased or the falling phase is prolonged, or both. Post-synaptic potentials are also affected by phenytoin. EPSPs are decreased in size, while the chloride-dependent, GABA-mediated IPSPs of the crayfish stretch receptor are prolonged. No effect was seen on chloride-dependent, ACh-mediated IPSPs in the abdominal ganglion of the Aplysia. Finally, phenytoin arrests endogenous or pharmacologically induced bursting. Most of the described effects are consistent with the antiarrhythmic and antiepileptic properties of the drug.

Action Potentials↗

In vitro neurophysiology of identified rat hypothalamic 'neuroendocrine' neurons.

Stable synaptic and antidromic electrophysiological recordings were obtained for 10-15 h from identified neurohypophyseal and tuberoinfundibular neurons using an acute explant of rat hypothalamus maintained in vitro through perfusion of the carotid artery with oxygenated artificial media. Synaptic potentials from preoptic and median eminence stimulation were blocked during perfusion with 12 m M Mg++-containing solutions. Antidromic and spontaneous action potentials recorded in neurohypophyseal neurons were followed by a transient after-hyperpolarization of 3-10 mV, due primarily to a brief increase in potassium conductance. Evidence favoring the existence of a synaptic recurrent inhibitory pathway was present in records obtained from tuberoinfundibular neurons, but not from neurohypophyseal cells.

Animals↗

Excitatory synaptic drive for swimming mediated by amino acid receptors in the lamprey.

In order to investigate the properties and pharmacology of the excitatory synaptic drive received by motoneurons during swimming in the lamprey, propriospinal excitatory interneurons were activated as a population by the regional application of N-methyl-D,L-aspartate (NMA) to either the 6-8 rostral-most or the 6-8 caudal-most segments of lengths of isolated spinal cord. This caused a rhythmic motor output to be generated in these regions. Synaptic potentials that were phase-locked to, and dependent on, the rhythmic motor activity of the segments exposed to the agonist could be recorded in motoneurons lying outside the activated regions. The synaptic drive to motoneurons located rostral or caudal to the activated regions was studied. Motoneurons received both descending and ascending synaptic input, which consisted of alternating excitatory and inhibitory phases. The inhibition could be reversed by chloride injection and blocked by strychnine, leaving an oscillating excitatory phase. The descending excitatory drive could extend 1-9 segments from the active region, while the ascending excitatory drive was recorded only in motoneurons that were 1-3 segments rostral to the active region. Both types of drive occurred in phase with the ipsilateral ventral root discharge: The peak depolarization of the descending drive occurred at the same point in the swimming cycle as that of the depolarizing phase seen during fictive swimming, while that of the ascending drive occurred significantly later. Both ascending and descending drives were partially reduced in amplitude by 2-amino-5-phosphonovaleric acid or Mg2+. The blocking action of Mg2+ was, in both cases, voltage dependent. Cis-2,3-piperidine dicarboxylic acid or kynurenic acid caused a much greater reduction in the amplitude of the oscillations. These results suggest that a major part of the excitatory drive for swimming in lamprey motoneurons is generated by populations of propriospinal interneurons with relatively long descending and/or short ascending axons, which fire rhythmically during swimming and release an amino acid transmitter that excites motoneurons through N-methyl-D-aspartate (NMDA) and non-NMDA receptors. This information will allow these important neurons to be identified in future experiments.

Afferent Pathways↗

Actions of substance P on rat spinal dorsal horn neurones.

The membrane actions of substance P (SP) and the effects on the Ca-dependent action potential of dorsal horn neurones have been investigated by means of intracellular recording techniques in the immature rat in vitro spinal cord slice preparation. Bath application of SP (2 X 10(-6) to 1 X 10(-5) M) induced a biphasic membrane response consisting of an initial hyperpolarization followed by a depolarization in about one-third of the cells examined. Initial hyperpolarization was not observed when synaptic activity was blocked by perfusing the slice with a tetrodotoxin-containing or low Ca, high Mg Ringer solution. This result is consistent with a presynaptic action of SP mediated through excitation of inhibitory interneurones. This interpretation was supported by recording of repetitive spontaneous inhibitory post-synaptic potential (i.p.s.p.)-like hyperpolarizing potentials during the initial hyperpolarization. When Co ions were used to block voltage-dependent Ca conductance and possible indirect presynaptic actions, SP induced only a small depolarization of membrane potential. It seems, therefore, that Ca conductance may have contributed to the depolarizing phase of the SP response, either through its mediation of synaptic transmission or through direct effects as a charge carrier for inward current. When tetrodotoxin was used, the SP-induced increase in neuronal input resistance was not modified, although depolarization was slightly diminished. In contrast, in medium containing tetrodotoxin and tetraethylammonium, the SP-depolarizing response was enhanced and accompanied by a small decrease in input resistance and firing of Ca spikes. These results suggest that SP-induced depolarization might be a consequence of a reduction in a voltage-dependent K conductance allowing Na and/or Ca conductances to dominate. SP modified the duration of Ca-dependent action potentials of dorsal horn neurones, the most consistent change being an initial dose-dependent and reversible decrease in the spike duration. The decrease in Ca spike duration was associated with a small reduction in the rate of rise and peak amplitude, and a significant parallel increase in dV/dt of the falling phase of the Ca spike. Our data indicate that the initial decrease in Ca spike duration was not due to the depolarizing action of SP, although shunting of the membrane resistance, either through presynaptic or post-synaptic mechanisms, has not been ruled out. Alternatively, these data are consistent with the possibility that SP shortens the duration of the Ca spike by decreasing a voltage-sensitive inward Ca current and/or augmenting an outward K current.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Effects of the combination of halothane and serotonin uptake blockers on synaptic transmission in the rat dentate gyrus in vitro.

Although the exact basis of their action remains unknown, volatile agents affect noradrenergic and serotoninergic systems. Imipramine and fluoxetine have documented effects on these neurotransmitter transmission systems. Given the common sites of action of these antidepressants and halothane, we examined their individual and combined effects on tonic excitatory post-synaptic potentials (EPSPs) and frequency dependent blockade in the rat dentate gyrus in vitro. Extracellular recordings of field EPSPs were maintained from the dentate gyrus, in the presence of picrotoxin (100 microM). Stimulation at 30 Hz (200 ms) allowed investigation of frequency dependent blockade. Once a stable equilibrium was established, halothane, imipramine and fluoxetine were administered via the perfusate and recordings were made. Halothane produced a dose dependent reduction in EPSP amplitude (EC50 0.28 mM; n = 12). Imipramine (1-10 microM) potentiated the EPSP amplitude (148.2 +/- 8.2%; imipramine 1 microM; n = 6). Fluoxetine (0.5-10 microM) reduced EPSP amplitude to 83.7 +/- 22.1% of control (n = 6). In the presence of halothane 0.2 mM, imipramine reduced the EPSP amplitude to 56.5 +/- 9.9% of control (imipramine 10 microM; n = 6; p < 0.05 compared with imipramine alone). Halothane (0.2 mM) demonstrated frequency dependent blockade. However, neither imipramine nor fluoxetine showed use dependent inhibition at the doses investigated. When combined with halothane 0.2 mM, fluoxetine 10 microM demonstrated frequency dependent blockade at the sixth pulse in the train compared with controls (13.8 +/- 4.7% vs 38.1 +/- 8.3%; n = 6; p < 0.05). The halothane-imipramine combination did not exhibit use dependent blockade greater than controls. The reversal of imipramine-induced EPSP potentiation by the preapplication of halothane has not been previously reported. It may be due to modulation of noradrenergic transmission by halothane. The frequency dependent blockade produced by the combination of fluoxetine 10 microM and halothane may be mediated by a nonspecific membrane effect on 5-HT uptake. These differing effects underline the broad action of volatile agents on synaptic mechanisms.

Anesthetics, Inhalation↗

Repeated ECS and fluoxetine administration have equivalent effects on hippocampal synaptic plasticity.

RATIONALE: Recent studies have implicated intracellular transduction pathways and neurotrophic factors in the action of antidepressants. Adaptation in these pathways may ultimately affect electrophysiological and morphological properties of neurones. We have previously shown that repeated electroconvulsive stimulation, a safe and effective antidepressant treatment, has profound effects on hippocampal synaptic connectivity and plasticity in the rat. Here, we investigated whether these electrophysiological properties were shared by the chemical antidepressant, fluoxetine. OBJECTIVES: To compare the electrophysiological and cognitive effects of two very different antidepressant treatments: repeated electroconvulsive stimulation (rECS); and chronic administration of the serotonin specific re-uptake inhibitor (SSRI), fluoxetine. METHODS: Rats were exposed to either rECS or daily fluoxetine administration for 15 days. The animals were then anaesthetised and dentate field excitatory post-synaptic potential (fEPSP) characteristics were measured before and after the induction of long-term potentiation (LTP) by high frequency perforant path stimulation. In a separate experiment, the effects of rECS and chronic fluoxetine administration on acquisition and retention of a spatial learning task in the Morris watermaze were determined. RESULTS: Chronic fluoxetine administration and rECS produced equivalent increases in dentate fEPSP compared to respective control groups. LTP induction was attenuated in both groups. Spatial learning was, in contrast, unaffected by fluoxetine treatment but significantly impaired following rECS. CONCLUSIONS: Given that fluoxetine and rECS share antidepressant properties, but differ in their effects on learning and memory, we propose that the common effects on dentate connectivity and synaptic plasticity described here are more likely to relate to affective rather than cognitive function. This result is consistent with other experiments showing that a reduction in dentate connectivity correlates with stress susceptibility in animals.

Animals↗

Optical imaging of cytosolic calcium, electrophysiology, and ultrastructure in pyramidal neurons of organotypic slice cultures from rat hippocampus.

Organotypic slice cultures from rat hippocampal cortex grown in an interface between culture medium and a CO2-enriched atmosphere maintained much of the morphological connectivity characteristic of the hippocampus in situ and thinned out considerably, facilitating optical measurements of fluorescent dyes sensitive to Ca2+ in individual neurons. Pyramidal neurons of the CA3 region presented morphological features of differentiated cells, including complex dendritic arborization and large numbers of dendritic spines. The fine cytoskeletal substructure at the postsynaptic density, below the plasma membrane, and within the core of the head and neck of dendritic spines in rapidly frozen slice cultures presents the characteristic morphology previously described for Purkinje cell dendritic spines in acutely dissected cerebellar cortex slices after rapid freezing. CA3 neurons responded to intracellular current injection with a train of action potentials, spike frequency adaptation, and a slow afterhyperpolarization. These spike trains caused rapid increases in dendritic [Ca2+]i that decayed to resting levels after termination of the current pulse. Dendritic spines were clearly observed in proximal dendrites of CA3 neurons in live preparations. [Ca2+]i transients in these dendritic spines closely followed the changes observed in the main dendritic shaft. Orthodromic synaptic stimulation from the dentate hilus generated long-lasting synaptic potentials accompanied by large [Ca2+]i transient in CA3 pyramidal neurons. The [Ca2+]i response was first observed in the proximal dendrites, after which the soma exhibited a [Ca2+]i increase, returning to resting levels within 10 s after the synaptic stimulus. Slice cultures thus provide a favorable opportunity to investigate [Ca2+]i responses in individual neurons maintained in an organotypic synaptic environment, taking advantage of high-resolution optical techniques.

Animals↗

On the action of the anticonvulsant 5,5-diphenylhydantoin and the convulsant picrotoxin in crayfish stretch receptor.

1. The effects of the anticonvulsant drug 5,5-diphenylhydantoin (DPH) and the convulsant drug picrotoxin (PTX) on various membrane properties and GABA-ergic inhibition were investigated in the slowly adapting neurone of the isolated crayfish stretch receptor. The soma was penetrated with two micro-electrodes to allow accurate determination of membrane conductances. 2. Neither DPH nor PTX at 10(-4) M had any significant effect on parameters of the anti- or orthodromic action potential or on the amplitude and duration of post-tetanic hyperpolarization. This suggests that the pharmacological properties of the two drugs are unlikely to be mediated by effects on cationic movements in this preparation. 3. DPH increased the amplitude and duration of the inhibitory post-synaptic potential (i.p.s.p.) within the range 10(-9) to 10(-4) M. The response to ionophoretically applied GABA was similarly prolonged. 4. PTX decreased the amplitude of the i.p.s.p. and prolonged its rising phase within the range 10(-8) to 10(-4) M. The response to ionophoretically applied GABA was similarly depressed. 5. A slow component of fluctuations in the resting potential was accentuated by DPH at 10(-4) M and eliminated by PTX 10(-4) M. This may reflect effects on the random opening and closing of inhibitory channels. 6. We conclude that the action of both drugs is post-synaptic and suggest that DPH decreases the probability of closing, and PTX the probability of opening, of the transmitter-activated channels. 7. The lack of any structural similarity between the two drugs suggests that they modify post-synaptic inhibition at separate sites. These sites appear to be interdependent since analysis of the shift in the DPH dose-response curve by PTX and vice versa, showed neither truly non-competitive nor competitive interaction.

Action Potentials↗