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Contrast affects the transmission of visual information through the mammalian lateral geniculate nucleus.

1. We recorded with one electrode action potentials of single principal cells in the lateral geniculate nucleus (l.g.n.) of cats and monkeys, together with their retinal inputs, recorded as synaptic potentials (S potentials; Bishop, Burke & Davis, 1958; Cleland, Dubin & Levick, 1971; Kaplan & Shapley, 1984). 2. We studied the effect of stimulus contrast on the transmission of visual information from the retina to the l.g.n., compared the spontaneous discharge of l.g.n. cells with that of their retinal inputs, and studied the driven (modulated) and maintained (unmodulated) discharge of l.g.n. neurones and their retinal drives. 3. The spontaneous discharge of l.g.n. cells was considerably lower than that of their retinal drives. 4. The maintained (unmodulated) discharge of l.g.n. cells during stimulation was lower than that of their retinal drives, and was largely unaffected by the stimulus contrast. 5. The responses of both the retinal input and l.g.n. cells increased with contrast, but at different rates: a given increment of contrast caused a larger increment of response in the retinal input than in the l.g.n. target cells. 6. The transmission ratio (l.g.n. response/retinal response) for most cells depended upon the stimulus contrast. This dependence indicates the presence of a non-linear contrast gain control. 7. The amount by which the l.g.n. attenuated the retinal input depended upon the temporal frequency, and, to a lesser extent, upon the spatial frequency of the stimulus. 8. The effect of contrast on signal transmission between the retina and l.g.n. was essentially the same in the macaque monkey as in the cat. 9. The attenuation of the retinal input by the l.g.n. contrast gain control could serve to prevent saturation and extend the dynamic range of cortical units, which probably receive input from several l.g.n. units.

Action Potentials↗

Systemic administration of lentinan, a branched beta-glucan, enhances long-term potentiation in the rat dentate gyrus in vivo.

We investigated the effects of oral and intravenous application of lentinan, a branched beta-glucan, on the induction of long-term potentiation (LTP) in the rat dentate gyrus in vivo. Oral administration of lentinan (200 mg/kg) enhanced the induction of LTP evoked by sub-threshold tetanic stimulation (20 pulses at 60 Hz) of the perforant pathway without affecting normal synaptic potentials. Intravenous injection of the compound (0.2-10.0 mg/kg) also enhanced the induction of LTP in a bell-shaped manner, whereas it had no effect on LTP evoked by supra-threshold tetanic stimulation (100 pulses at 100 Hz). Structurally related beta-glucans did not mimic the lentinan-triggered enhancement of LTP. These results suggest that peripherally applied lentinan facilitates the synaptic efficacy of the dentate gyrus neurons in vivo.

Adjuvants, Immunologic↗

Learning induces long-term potentiation in the hippocampus.

Years of intensive investigation have yielded a sophisticated understanding of long-term potentiation (LTP) induced in hippocampal area CA1 by high-frequency stimulation (HFS). These efforts have been motivated by the belief that similar synaptic modifications occur during memory formation, but it has never been shown that learning actually induces LTP in CA1. We found that one-trial inhibitory avoidance learning in rats produced the same changes in hippocampal glutamate receptors as induction of LTP with HFS and caused a spatially restricted increase in the amplitude of evoked synaptic transmission in CA1 in vivo. Because the learning-induced synaptic potentiation occluded HFS-induced LTP, we conclude that inhibitory avoidance training induces LTP in CA1.

Animals↗

Somatostatin regulates excitatory amino acid receptor-mediated fast excitatory postsynaptic potential components in vagal motoneurons.

Somatostatin is considered to be a brain neurotransmitter/neuromodulator; however, there is little concrete information on how this peptide contributes to generation of synaptic potentials in the mammalian central nervous tissue. Recently, a well-defined somatostatin-containing pathway has been traced from the subnucleus centralis of the solitarial complex to the compact formation of the nucleus ambiguus. Moreover, we have demonstrated both in vivo and in vitro that somatostatin enhances glutamate but inhibits acetylcholine excitation of ambigual motoneurons, suggesting involvement of this peptide in central oesophagomotor transmission. The availability of a brainstem slice containing this pathway has allowed us to characterize an excitatory amino acid receptor-mediated excitatory postsynaptic potential in compact formation neurons. This excitatory postsynaptic potential is unusual because its rising phase involves activation of N-methyl-D-aspartate receptors. Here we report that somatostatin participates in ambigual excitatory postsynaptic potential generation by permitting expression of the N-methyl-D-aspartate receptor-mediated component, thereby regulating fast information transfer in this pathway.

Animals↗

Functional, structural and chemical correlates of sprouting of intact preganglionic sympathetic axons in the guinea-pig.

Intact preganglionic axons can sprout and form new functional synaptic connexions with neurones in the partially denervated superior cervical ganglion of the guinea-pig (Maehlen & Njå, 1981). In the present work we have examined to what extent the degree of sprouting, as measured by intracellular recording, is paralleled by changes in ultrastructural and neurochemical parameters. The mean number of preganglionic axons innervating each neurone, as estimated by intracellular recording from ganglion cells during stimulation of the individual ventral roots, was reduced from about eleven to about two immediately after the partial denervation. However, 5-7 weeks after the operation, when sprouting was complete, each neurone was innervated on average by about seven axons. The estimated mean amplitude of the synaptic potential elicited by each innervating axon (about 5 mV) was only slightly increased after sprouting. Counts of the number of synaptic profiles per unit area of electron microscopical sections of the ganglion were reduced to about 15% of normal 3-4 days after the operation, and increased to about 60% of normal after sprouting (5-7 weeks). The activity of the enzyme choline acetyltransferase was about 20% of the normal value in ganglia examined 3-4 days after partial denervation. After sprouting (5-7 weeks), this value was increased to about 35% of that in normal ganglia. These results show that intact preganglionic sympathetic axons have a substantial growth potential. However, the increase in the choline acetyltransferase activity was smaller than the increase in electrophysiological and ultrastructural measurements. Therefore, compensatory axonal branching and synapse formation may cause a reduction in the supply of choline acetyltransferase to each presynaptic terminal from the parent soma.

Animals↗

Computational model of carbachol-induced delta, theta, and gamma oscillations in the hippocampus.

Field potential recordings from the rat hippocampus in vivo contain distinct frequency bands of activity, including delta (0.5-2 Hz), theta (4-12 Hz), and gamma (30-80 Hz), that are correlated with the behavioral state of the animal. The cholinergic agonist carbachol (CCH) induces oscillations in the delta (CCH-delta), theta (CCH-theta), and gamma (CCH-gamma) frequency ranges in the hippocampal slice preparation, eliciting asynchronous CCH-theta, synchronous CCH-delta, and synchronous CCH-theta with increasing CCH concentration (Fellous and Seinowski, Hippocampus 2000;1 0:187-197). In a network model of area CA3, the time scale for CCH-delta corresponded to the decay constant of the gating variable of the calcium-dependent potassium (K-AHP) current, that of CCH-theta to an intrinsic subthreshold membrane potential oscillation of the pyramidal cells, and that of CCH-gamma to the decay constant of GABAergic inhibitory synaptic potentials onto the pyramidal cells. In model simulations, the known physiological effects of carbachol on the muscarinic and K-AHP currents, and on the strengths of excitatory postsynaptic potentials, reproduced transitions from asynchronous CCH-theta to CCH-delta and from CCH-delta to synchronous CCH-theta. The simulations also exhibited the interspersed CCH-gamma/CCH-delta and CCH-gamma/CCH-theta that were observed in experiments. The model, in addition, predicted an oscillatory state with all three frequency bands present, which has not yet been observed experimentally.

Acetylcholine↗

Primary afferent excitatory transmission recorded intracellularly in vitro from rat medial vestibular neurons.

Intracellular recordings were made from rat medial vestibular nucleus (MVN) neurons in transverse brain slices containing the root of the vestibular nerve (N. VIII). Electrical stimuli applied to the N. VIII tract evoked an orthodromic excitatory postsynaptic potential (EPSP) that lasted about 50 ms following a 0.5 to 1.5 ms delay between the stimulus artifact and synaptic potential. These orthodromic EPSPs were insensitive to the following antagonists: atropine, hexamethonium, diphenhydramine, and caffeine. Based on these results we conclude that the primary afferent excitatory transmitter is not acetylcholine, histamine, or adenosine, respectively. However, kynurenic acid, a general excitatory amino acid receptor antagonist, blocked the orthodromic EPSP while having no effect on the resting membrane potential, input resistance, or action potential configuration of MVN neurons. Our data suggest that an excitatory amino acid, or amino acid-like substance, is responsible for primary afferent excitatory transmission in the rat medial vestibular nucleus.

Action Potentials↗

Commissural and perforant path interactions in the rat hippocampus. Field potentials and unitary activity.

The interaction of the commissural and perforant path systems was studied by recording extracellular field potentials and single unit activity in the dentate gyrus in urethane-anesthetized rats. Conditioning commissural volleys suppressed extracellular synaptic potentials, population spikes and single unit discharges evoked by perforant path stimulation. Commissural stimulation (single or repetitive) failed to induce a population spike, however strong the stimulation. About half of the cells fired monosynaptically to perforant path volleys and 20% to commissural volleys. Half of the commissurally driven units fired before or coincided with field potential onset. The antidromic mechanism of these short latency unitary spikes was shown by the collision test. Commissural activation reduced spontaneous cell firing without previous excitation in 25% of the neurons. Less than 6% of the cells responded to stimulation of both inputs, indicating little convergence between the two pathways. We contend that a simple from of recurrent inhibition fails to explain the above findings, and the possibility of feed-forward inhibition by commissural activation has been raised.

Afferent Pathways↗

Requirement of basolateral amygdala neuron activity for the induction of long-term potentiation in the dentate gyrus in vivo.

We investigated the effect of injection of a local anesthetic, tetracaine, into the ipsilateral basolateral amygdala (BLA) on long-term potentiation (LTP) in the medial perforant path-dentate gyrus granule cell synapses of anesthetized rats. The dentate gyrus synaptic potential evoked by low frequency test stimulation did not change following tetracaine injection into BLA. However, when tetanic stimulation (30 pulses at 60 Hz) was applied 10 min after tetracaine injection, the magnitude of LTP was significantly attenuated in a dose-dependent manner. Injection of tetracaine after tetanic stimulation did not affect the established LTP. The small LTP observed in the BLA-lesioned rats was regarded as the BLA-independent component of LTP, which was not affected by tetracaine injection. These results suggest that neuron activities in the ipsilateral BLA are partly required for the induction of LTP in the dentate gyrus in vivo.

Amygdala↗

The action potential of chick dorsal root ganglion neurones maintained in cell culture.

1. The directly evoked action potential of dissociated, embryonic, chick, dorsal root ganglion (DRG) neurones maintained in cell culture is prolonged compared to spinal cord cell spikes and the re-polarization phase is marked by a plateau. 2. Evidence was obtained that both Ca2+ and Na+ carry inward current across the active soma membrane. Ca2+ because: overshooting spikes persist in tetrodotoxin (TTX) or Na+-free media; in the presence of TTX (or absence of Na+) spike size varies directly with extracellular Ca2+ and spikes are eliminated by Co2+. Na+ because: spikes persist in the presence of Co2+ or Ca2+-free media; in the presence of Co2+ (or absence of Ca2+) spike varies directly with extracellular Na+ and spikes are blocked by TTX. 3. On the other hand, Ca2+ plays less if any role in action potentials conducted along sensory nerve cell processes. Conducted spikes could not be evoked in TTX containing or Na+-free media. 4. A long-lasting depolarization follows the action potential in some neurones. This depolarization is associated with an increase in membrane conductance and appears to drive the membrane potential to ca. -30mV. It persists when conducted impulses are blocked so it is probably not a recurrent synaptic potential. 5. It is suggested that combined Ca2+-Na+ spikes observed in isolated sensory neurones in vitro reflect the action potential of adult sensory cells but the possibility that they represent an early stage in development is also discussed.

Action Potentials↗

Electrophysiology and enkephalin immunoreactivity of identified myenteric plexus neurones of guinea-pig small intestine.

Intracellular injection of the fluorescent dye, Lucifer Yellow CH, revealed the shapes of neurones in the myenteric plexus of the guinea-pig ileum, and these shapes were correlated with the electrophysiological properties and enkephalin immunoreactivity of the neurones. A total of eighty-three neurones were filled using electrodes containing a 5% solution of the dye. Forty-six cells had many short processes and a single long process (Dogiel type 1) and twenty-four cells had essentially smooth somas and one to eight long processes (Dogiel type II). Thirteen cells could not be put into either group. Enkephalin-like immunoreactivity was detected in twenty-two of the forty-six Dogiel type I cells. Eighteen of these had club-like short processes. No other cells of the eighty-three showed enkephalin-like immunoreactivity. Electrodes filled with a 0.5% solution of Lucifer Yellow in 0.5 M-KCl were used to record from and simultaneously to inject dye into 240 neurones. Eighty-six nerve cells had a slow after-hyperpolarization following the action potential (AH cells) and forty-six nerve cells had no after-hyperpolarization but exhibited a fast excitatory synaptic potential (S cells). The other cells could not be unequivocally identified by their observed electrophysiological characteristics. Almost all S cells (forty-two of forty-six) were Dogiel type I, while eighty-two of the eighty-six AH cells were Dogiel type II. Fifty S cells (eight located geometrically, forty-two by dye injection) and ninety-one AH cells (twenty-six located geometrically, sixty-five by dye injection) were examined for enkephalin immunoreactivity. Fifteen of the S cells were reactive, whereas all of the AH cells were unreactive. It appears that prolonged impalements reduce immunoreactivity so that the proportion of reactive neurones in this series is an underestimate of the true proportion of S cells with enkephalin-like immunoreactivity. The results suggest that a substantial proportion of the S cells in myenteric ganglia contain enkephalin immunoreactivity while none of the AH cells do. The enkephalin neurones have a distinctive shape and are all Dogiel type I cells. AH cells are nearly always Dogiel type II.

Action Potentials↗

Swallowing-related perihypoglossal neurons projecting to hypoglossal motoneurons in the cat.

Although previous studies have examined the functional role of the neurons in the area ventrolateral to the hypoglossal nucleus (perihypoglossal neurons) in the trigemino-hypoglossal reflex, no convincing evidence for the direct connection from the perihypoglossal neurons to the hypoglossal motoneurons has yet been provided. In addition, the role of the perihypoglossal neurons in swallowing has not been studied. The purpose of this study was to investigate (1) the input-output relationship of the perihypoglossal neurons and (2) whether the afferent feedback was essential for their swallowing-related activity in chloralose-anesthetized cats. Before and after the cats were paralyzed, single-unit activities were recorded extracellularly from 30 perihypoglossal neurons during swallowing elicited by electrical stimulation of the superior laryngeal nerve. These perihypoglossal neurons responded with spike potentials after short latencies to stimulation of the inferior alveolar and hypoglossal nerves. The neurons also responded with spike potentials to single shocks applied to the superior laryngeal nerve, but were activated transiently at the initial phase of repetitive stimulation of the nerve and kept silent until the occurrence of swallowing before and after the animal was paralyzed. They showed burst activities in coincidence with swallowing. Averaging of intracellular potentials of a hypoglossal motoneuron by simultaneously recorded extracellular spikes of a perihypoglossal neuron revealed monosynaptic inhibitory post-synaptic potentials. We conclude that, in the region ventrolateral to the hypoglossal nucleus, there are neurons which relay trigeminal, hypoglossal, and vagal afferents. Furthermore, some of these perihypoglossal neurons are inhibitory hypoglossal premotor neurons that are involved in the central programming of swallowing.

Afferent Pathways↗

Short-term effects of adolescent methylphenidate exposure on brain striatal gene expression and sexual/endocrine parameters in male rats.

Exposure to methylphenidate (MPH) during adolescence is the elective therapy for attention deficit/hyperactivity disorder (ADHD) children, but raises major concerns for public health, due to possibly persistent neurobehavioral changes. Rats (30- to 44-days old) were administered MPH (2 mg/kg, i.p once daily) or saline (SAL). At the end of the treatment we collected plasma, testicular, liver, and brain (striatum) samples. The testes and liver were used to evaluate conventional reproductive and metabolic endpoints. Testes of MPH-exposed rats weighed more and contained an increased quantity of sperm, whereas testicular levels of testosterone (TST) were markedly decreased. The MPH treatment exerted an inductive effect on enzymatic activity of TST hydroxylases, resulting in increased hepatic TST catabolism. These findings suggest that subchronic MPH exposure in adolescent rats could have a trophic action on testis growth and a negative impact on TST metabolism. We have analyzed striatal gene expression profiles as a consequence of MPH exposure during adolescence, using microarray technology. More than 700 genes were upregulated in the striatum of MPH-treated rats (foldchange >1.5). A first group of genes were apparently involved in migration of immature neural/glial cells and/or growth of novel axons. These genes include matrix proteases (ADAM-1, MMP14), their inhibitors (TIMP-2, TIMP-3), the hyaluronan-mediated motility receptor (RHAMM), and growth factors (transforming growth factor-beta3 [TGF-beta3] and fibroblast growth factor 14 [FGF14]). A second group of genes were suggestive of active axonal myelination. These genes mediate survival of immature cells after contact with newly produced axonal matrix (laminin B1, collagens, integrin alpha 6) and stabilization of myelinating glia-axon contacts (RAB13, contactins 3 and 4). A third group indicated the appearance and/or upregulation of mature processes. The latter included genes for: K+ channels (TASK-1, TASK-5), intercellular junctions (connexin30), neurotransmitter receptors (adrenergic alpha 1B, kainate 2, serotonin 7, GABA-A), as well as major proteins responsible for their transport and/or anchoring (Homer 1, MAGUK MPP3, Shank2). All these genes were possibly involved in synaptic plasticity, namely the formation, maturation, and stabilization of new neural connections within the striatum. MPH treatment seems to potentiate synaptic plasticity, which is an age-dependent developmental phenomenon that adolescent rats are very likely to show, compared to adults. Our observations suggest that adolescent MPH exposure causes only transient changes in reproductive and hormonal parameters, and a more enduring enhancement of neurobehavioral plasticity.

Animals↗

Stress, corticosteroid hormones and hippocampal synaptic function.

Exposure to stressful events has profound impact on hippocampus-dependent learning and memory processes. Traumatic and stressful experiences are remembered well in general, but have also been reported to suppress learning and memory processes. These bi-directional effects are, at least in part, modulated by corticosteroid hormones that are released during exposure to stressful experiences. An important question that remains to be addressed is how exactly exposure to stressful situations and elevated corticosteroid hormone levels affect learning and memory processes. Evidence is accumulating that exposure to stressful situations and elevated corticosteroid hormone levels modulates fast excitatory amino acid mediated synaptic transmission and synaptic plasticity, which are considered to underlie learning and memory processes in the hippocampus. In particular, exposure to stressful events has been reported to facilitate synaptic plasticity when delivered shortly before or after high frequency stimulation. By contrast, stressful events and elevated corticosteroid hormones suppress synaptic potentiation when stress precedes high frequency stimulation. From the mechanistic point of view, it is potentially important that exposure to stressful events and elevated corticosteroid hormone levels target key mechanisms that are involved in synaptic plasticity, i.e. AMPA receptors and NMDA receptors.

Adrenal Cortex Hormones↗

[Postactivation inhibition of processes in interneurons transmitting the activity of lateral "descending" systems].

After-discharge depression of excitability is found in the interneurons specialized on transmission of activities from "lateral" descending systems. Many of these cells are propriospinal units sending axons to the lateral funicle (LF). Anti- und orthodromic spike potentials in these cells are followed by significant hyperpolarization. In some cells post-activation depression increased with a rise in intensity of LF stimulation that evoked antidromic discharge; inhibitory post-synaptic potentials were recorded in several units after LF stimulation subthreshold for evoking such discharges. Existance of inhibitory synaptic connections between neurons of the investigated group similar to recurrent connections in the motoneuronal pools is supposed.

Action Potentials↗

Slow synaptic transmission in frog sympathetic ganglia.

Bullfrog ganglia contain two classes of neurone, B and C cells, which receive different inputs and exhibit different slow synaptic potentials. B cells, to which most effort has been directed, possess slow and late slow EPSPs. The sEPSP reflects a muscarinic action of acetylcholine released from boutons on B cells, whereas the late sEPSP is caused by a peptide (similar to teleost LHRH) released from boutons on C cells. During either sEPSP there is a selective reduction in two slow potassium conductances, designated 'M' and 'AHP'. The M conductance is voltage dependent and the AHP conductance is calcium dependent. Normally they act synergistically to prevent repetitive firing of action potentials during maintained stimuli. Computer stimulation of the interactions of these conductances with the other five voltage-dependent conductances present in the membrane allows a complete reconstruction of the effects of slow synaptic transmission on electrical behaviour.

Animals↗

An electrophysiological study of inferior mesenteric ganglion of the dog.

Intracellular recordings were made in vitro from 430 sympathetic neurons in the inferior mesenteric ganglion (IMG) of the dog. Ganglion cells had resting membrane potentials between -35 and -70 mV; input resistance (Rin) was approximately 22 M omega. Cell rheobase to depolarizing current was 0.3 nA, and the action potential elicited was 80-100 mV in amplitude followed by an afterhyperpolarization of up to 15 mV in size, which decayed to the resting membrane potential over a range of 50-500 ms. Neurons were classified as either phasic (188 of 280) or tonic (92 of 280) firing cells, depending on their discharge pattern in response to depolarizing current. Two hundred eight of 430 neurons showed continuous electrical activity in the form of spontaneous excitatory postsynaptic potentials, 2-5 mV in amplitude. Continuous electrical activity was unaffected by tetrodotoxin (3 X 10(-6) M) but abolished by hexamethonium (10(-4) M). A small number of cells (21 of 430) adopted a repetitive firing pattern not associated with injury discharge. These cells may have been pacemaking neurons. Stimulation of peripheral and central nerves resulted in multiple synaptic input to ganglion cells. There was marked convergence of excitatory fibers to any one cell. Evoked synaptic potentials were abolished by hexamethonium (10(-4) M). Synaptic input from peripheral and central nerves could not be correlated with location of postganglionic neurons in the IMG. The possibility of neuronal intercommunication and dissemination of central and peripheral commands is discussed.

Action Potentials↗