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PubMed1997

Diencephalic projection to reticulospinal neurons involved in the initiation of locomotion in adult lampreys Lampetra fluviatilis.

Morphological and electrophysiological techniques were used to characterize a diencephalic projection from the ventral thalamus to reticulospinal neurons and its role in initiating rhythmic locomotor activity in the spinal cord of adult lampreys (Lampetra fluviatilis). Injection of fluorescein-coupled dextran amine (FDA) into the rhombencephalic reticular nuclei labeled neurons in the ventral thalamus region on both the ipsilateral side and the contralateral side. Injection of FDA into the ventral thalamus labeled axonal projections in all reticular nuclei, but no direct projections were found to the spinal cord. Extracellular stimulation of the ventral thalamus elicited monosynaptic excitatory postsynaptic potentials (EPSPs), polysynaptic EPSPs, and inhibitory postsynaptic potentials (IPSPs) in reticulospinal neurons in the posterior (prrn) and middle (mrrn) rhombencephalic reticular nuclei. The monosynaptic EPSPs were blocked by the glutamate antagonist kynurenic acid and can be considered glutamatergic. The monosynaptic EPSPs were potentiated (up to 12 minutes) following a brief high-frequency stimulation. Stimulation of the ventral thalamus induced rhythmic firing of reticulospinal neurons and elicited rhythmic burst activity in the spinal ventral roots. The projections from the ventral thalamus to the reticulospinal neurons in the prrn and mrrn thus provide excitatory inputs to the reticulospinal neurons, which, in turn, can activate the spinal circuits underlying locomotion. Also, the input nuclei to the ventral thalamus were labeled following injection of FDA into this nucleus. Labeled cells were found in the olfactory bulb, pallial areas, striatum, preoptic nucleus, hypothalamus, dorsal thalamus, optic tectum, and dorsal isthmic gray. The ventral thalamus, therefore, receives inputs from several different regions in the brain and controls the level of excitability in reticulospinal neurons.

Animals↗
PubMed2005

Excitatory connections made by presynaptic cortico-cortical pyramidal cells in layer 6 of the neocortex.

Paired intracellular recordings with biocytin labelling were made in slices of adult rat somatosensory and visual cortex and in cat visual cortex to examine the properties of synaptic connections made by layer 6 pyramidal cells, to determine whether cortico-cortical pyramids more commonly provide input to other layer 6 pyramids than cortico-thalamic cells, and whether these connections exhibit paired pulse and brief train depression. Pyramidal cells with cortico-cortical like morphology were 2-4 times more likely to innervate other pyramidal cells than were cortico-thalamic like cells, but less likely to innervate inhibitory interneurons. The excitatory postsynaptic potentials elicited by presynaptic, phasically firing cortico-cortical pyramids in all classes of postsynaptic infragranular layer pyramidal cells exhibited strong, presynaptically mediated paired pulse and brief train depression. Those with larger paired pulse ratios also exhibited post-tetanic potentiation, but this was accompanied by stronger paired pulse and brief train depression. Both the firing characteristics and the outputs of cortico-cortical pyramidal cells display pronounced phasic characteristics, indicating that these cells respond most effectively to and preferentially pass on information related to novelty.

Animals↗
PubMed1994

Long-term depression in the hippocampal CA1 region is associated with equal changes in AMPA and NMDA receptor-mediated synaptic potentials.

In the CA1 hippocampal region low-frequency (1-2 Hz) afferent activation leads to a long-term depression of excitatory synaptic potentials that is induced by calcium influx through postsynaptic N-methyl-D-aspartate receptor channels. In the present experiments using 2- to 3-week-old rats, long-term depressions of field excitatory postsynaptic potentials mediated by amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and by N-methyl-D-aspartate receptor channels were examined in parallel, using a perfusion solution containing low concentrations of an AMPA receptor antagonist and of magnesium (0.1 mM). These experiments revealed that long-term depression was associated with equal relative changes in the two components of the field potential, compatible with a presynaptic location of the expression mechanism for the long-term depression.

Animals↗
PubMed2000

Bidirectional actions of docosahexaenoic acid on hippocampal neurotransmissions in vivo.

Docosahexaenoic acid (DHA), a 22-carbon fatty acid with six double bonds, is one of the major polyunsaturated fatty acids in fish oils or in the mammalian central nervous system and is believed to be essential for neuronal plasticity and development. In the present study, we evaluated the effect of DHA on hippocampal neurotransmissions using anesthetized rats. Field excitatory postsynaptic potential (fEPSP) evoked by stimulation of the Schaffer collaterals was recorded from the CA1 stratum radiatum. Following intracerebroventricular injection of DHA 25 nmol, the fEPSP slope decreased gradually in 30 min and was eventually suppressed by about 30%. On the other hand, when fEPSP was evoked by stimulation of the perforant path was recorded in the molecular layer of the dentate gyrus, an increase in fEPSP slope occurred over a similar time course after DHA injection. These phenomena were independent of N-methyl-D-aspartate receptor activity. Linoleic acid, one of polyunsaturated fatty acids, was virtually ineffective. Furthermore, we investigated the effect of DHA on hippocampal synaptic plasticity. Although DHA did not alter the profile of paired-pulse facilitation, it inhibited the induction of long-term potentiation in the CA1 area but not in the dentate gyrus. Thus, DHA exerts regionally different effects on hippocampal neurotransmission and may be a good tool for clarifying physiological functions of the hippocampus.

Animals↗
PubMed2006

Sustained elevation of extracellular adenosine and activation of A1 receptors underlie the post-ischaemic inhibition of neuronal function in rat hippocampus in vitro.

Adenosine is released from the compromised brain and exerts a predominately neuroprotective influence. However, the time-course of adenosine release and its relationship to synaptic activity during metabolic stress is not fully understood. Here, we describe experiments using an enzyme-based adenosine sensor to show that adenosine potently (IC50 approximately 1 microm) inhibits excitatory synaptic transmission in area CA1 during oxygen/glucose deprivation ('ischaemia'), and that the prolonged post-ischaemic presence of extracellular adenosine sustains the depression of the field excitatory postsynaptic potential (fEPSP). N-methyl-D-aspartate (NMDA) receptor antagonism promotes post-ischaemic recovery of the fEPSP, in parallel with reduced release of adenosine. Paradoxically, however, after ischaemia the fEPSP recovers in the face of concentrations of adenosine capable of fully eliminating synaptic transmission during ischaemia. This hysteresis is not prevented by NMDA receptor antagonism, is observed during repeated ischaemia when adenosine release is reduced, and does not reflect desensitization of adenosine A1 receptors. We conclude that adenosine exerts powerful inhibitory actions on excitatory synaptic transmission both during, and for some considerable time after, ischaemia. Therapeutic strategies designed to exploit both the continued presence of adenosine and activity of A1 receptors could provide benefits in individuals who have suffered acute injury to the CNS.

Adenosine↗
PubMed2006

Opiate withdrawal modifies synaptic plasticity in subicular-nucleus accumbens pathway in vivo.

Subiculum receives output of hippocampal CA1 neurons and projects glutamatergic synapses onto nucleus accumbens (NAc), the subicular-NAc pathway linking memory and reward system. It is unknown whether morphine withdrawal influences synaptic plasticity in the subicular-NAc pathway. Here, we recorded the field excitatory postsynaptic potential (EPSP) within the shell of NAc by stimulating ventral subiculum in anesthetized adult rats. We found that high frequency stimulation (HFS, 200 Hz) induced long-term potentiation (LTP) but low frequency stimulation (LFS, 1 Hz) failed to induce long-term depression (LTD) in control animals. However, behavioral stress enabled LFS to induce a reliable LTD (sLTD) that was dependent on the glucocorticoid receptors. Both LTP and sLTD were prevented by the N-methyl-d-aspartate receptor antagonist AP-5. After repeated morphine treatment for 12 days, acute withdrawal (12 h) impaired LTP but had no effect on sLTD; prolonged withdrawal (4 days) restored the LTP but impaired the sLTD. Remarkably, basal synaptic efficacy reflected by baseline EPSP amplitude was potentiated in acute withdrawal but was depressed in prolonged withdrawal. Thus, acute and prolonged opiate withdrawal may cause endogenous LTP and LTD in the subicular-NAc pathway that occludes the subsequent induction of synaptic plasticity, demonstrating adaptive changes of the NAc functions during opiate withdrawal.

Animals↗
PubMed1988

Propranolol blocks recurrent synaptic activation in paravertebral sympathetic ganglia of bullfrogs.

Intracellular recordings were made from neurons in bullfrog sympathetic ganglia. Orthodromic, intracellular and antidromic stimulations evoked recurrent depolarizing responses accompanied by a spontaneous firing of the action potential in type 2 neurons. The depolarizing response elicited by intracellular and antidromic stimulations was selectively blocked by propranolol (1 microM), but not by yohimbine and phenoxybenzamine. Propranolol did not block the 'nicotinic' fast excitatory postsynaptic potential evoked by orthodromic stimulation. These results suggest that excitatory beta-adrenoceptors mediate the recurrent synaptic facilitation of nicotinic transmission in type 2 neurons of bullfrog sympathetic ganglia.

Action Potentials↗
PubMed2003

The influence of developmental periods of sodium valproate exposure on synaptic plasticity in the CA1 region of rat hippocampus.

The effects of chronic sodium valproate (VPA) exposure during different developmental periods on synaptic plasticity were studied in the hippocampal CA1 area. Rats were exposed to VPA (300 mg/kg per day, intraperitoneal) over different developmental intervals: (1). prenatal exposure (PR group); (2). from parturition to weaning (PW group); (3). from pregnancy day 1 to weaning (PRW group). At postnatal day 22-28, field excitatory postsynaptic potentials were recorded in the CA1 area of hippocampal slices. We found that VPA exposure in the PR and PRW groups significantly impaired long-term potentiation (LTP), long-term depression (LTD) and paired-pulse facilitation (PPF). However, exposure during lactation (PW group) only impaired LTP and had no significant effect on LTD and PPF. These results suggested that VPA exposure during lactation had the least deficits on synaptic plasticity, while VPA exposure in the PR and PRW groups seriously impaired synaptic plasticity and should be avoided.

Animals↗
PubMed2002

Impaired acquisition in the water maze and hippocampal long-term potentiation after chronic prenatal ethanol exposure in the guinea-pig.

In the hippocampus, the CA1 region is selectively vulnerable to the effects of chronic prenatal ethanol exposure. In the guinea-pig, the number of CA1 pyramidal cells is decreased after chronic prenatal ethanol exposure. We tested the hypotheses that chronic prenatal ethanol exposure (through maternal ethanol ingestion) results in impairments in spatial learning and short- and long-term plasticity in the CA1 region of the postnatal guinea-pig hippocampus. Timed, pregnant guinea-pigs were treated with ethanol (4 g/kg maternal body weight/day), isocaloric sucrose/pair-feeding, or water throughout gestation. Offspring were studied between postnatal days 40 and 80. In the Morris water maze, animals exposed to ethanol prenatally showed slower acquisition of an escape response to a hidden platform over 5 days of training. The amplitude of the field excitatory postsynaptic potential in the CA1 region in response to contralateral CA3 stimulation was decreased in offspring exposed to ethanol prenatally. Two forms of short-term plasticity (paired-pulse and frequency facilitation) were unaffected by chronic prenatal ethanol exposure. Long-term potentiation (LTP) in response to high-frequency CA3 stimulation was induced reliably and maintained over 60 min in isocaloric-sucrose and water control animals. However, LTP failed to be induced in the CA1 area of the hippocampus in prenatal ethanol-exposed offspring. These data show that chronic prenatal ethanol exposure, through maternal ethanol administration, impairs spatial performance and LTP in CA1 neurons. Hippocampal dysfunction could contribute importantly to the cognitive and behavioural deficits resulting from chronic prenatal ethanol exposure.

Alcohol-Induced Disorders, Nervous System↗
PubMed2004

Novel method for quantification of brain cell swelling in rat hippocampal slices.

We have developed a novel device for the quantification of edematous morphology changes in acute brain slices. We can also carry out real-time monitoring of detailed hippocampal cells. The device we developed is based on infrared differential interference contrast microscopy (IR-DIC) and a custom-made real-time computerized image-analysis system for quantification of the morphological dynamics of cells in slice preparations. We applied the coefficient of variation (CV) of light intensity in IR-DIC images to evaluate the change in morphological dynamics. We examined three kinds of edema in the CA1 region of rat hippocampal acute slices under conditions of hypotonic, strong excitation, and experimental ischemia, together with field excitatory postsynaptic potential (fEPSP) recording from radiatum in CA1 the region. There were notable close relationships among the edema formations, the light transmittance, the extent of changes in CV, and features of fEPSP during the three different insults. The present results indicate that CV is a reliable quantification index for edema formation in brain tissue and confirm that applying CV for the analysis in addition to the light transmittance analysis presents additional important information on brain tissue swelling.

Animals↗
PubMed2004

Specific functions of Drosophila amyloid precursor-like protein in the development of nervous system and nonneural tissues.

Drosophila amyloid precursor-like protein (APPL) is expressed extensively in the nervous system soon after neuronal differentiation. By utilizing different transgenic flies, we studied the physiological function of two APPL protein forms, membrane-bound form (mAPPL) and secreted form (sAPPL), in neural development. We found that neither deletion nor overexpression of APPL protein altered the gross structure of mushroom bodies in the adult brain. No changes were detected in cell types and their relative ration in embryo-derived cultures from all APPL mutants. However, the neurite length was significantly increased in mutants overexpressing mAPPL. In addition, mutants lacking sAPPL had numerous neurite branches with abnormal lamellate membrane structures (LMSs) and blebs, while no apoptosis was detected in these neurons. The abnormal neurite morphology was most likely due to the disorganization of the cytoskeleton, as shown by double staining of actin filaments and microtubules. Electrophysiologically, A-type K+ current was significantly enhanced, and spontaneous excitatory postsynaptic potentials (sEPSPs) were greatly increased in APPL mutants lacking sAPPL. Moreover, panneural overexpression of different forms of APPL protein generated different defects of wings and cuticle in adult flies. Taken together, our results suggest that both mAPPL and sAPPL play essential roles in the development of the central nervous system and nonneural tissues.

Actin Cytoskeleton↗
PubMed2006

Hyperpolarization-activated and cyclic nucleotide-gated cation channel subunit 2 ion channels modulate synaptic transmission from nociceptive primary afferents containing substance P to secondary sensory neurons in laminae I-IIo of the rodent spinal dorsal horn.

We have previously demonstrated that hyperpolarization-activated and cyclic nucleotide-gated cation channel subunit 2 (HCN2) is expressed by terminals of peptidergic nociceptive primary afferents in laminae I-IIo of the rat spinal dorsal horn. In this study, we investigated the possible neurotransmitters and postsynaptic targets of these HCN2-expressing primary afferent terminals in the superficial spinal dorsal horn by using immunocytochemical methods. We demonstrated that HCN2 widely colocalizes with substance P (SP), and that HCN2-positive terminals that are also immunoreactive for SP form serial close appositions with dendrites and perikarya of neurokinin 1 receptor-immunoreactive neurons. It was also found that HCN2-immunoreactive terminals are frequently apposed to neurons that are immunoreactive for calbindin, micro-opioid receptor and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunit GluR2, markers for excitatory interneurons. Investigating HCN2 immunoreactivity in glutamic acid decarboxylase 65-green fluorescent protein transgenic mice, we found that HCN2-positive terminals occasionally also contact cells that contain an isoform of glutamic acid decarboxylase (glutamic acid decarboxylase 65), a marker for GABAergic inhibitory neurons. Application of ZD7288, an antagonist of HCN channels, onto neurons that were recorded in spinal cord slices with whole-cell patch-clamp electrodes reduced the number of monosynaptic excitatory postsynaptic potentials evoked by electrical stimulation of primary afferents at nociceptive intensities. The results suggest that HCN2 may contribute to the modulation of membrane excitability of SP-containing nociceptive primary afferent terminals, may increase the reliability of synaptic transmission from primary afferents to secondary sensory neurons and thus may play a role in the fine-tuning of pain transmission from nociceptive primary afferents to neurons in the spinal dorsal horn.

Afferent Pathways↗
PubMed2003

Hypocretinergic facilitation of synaptic activity of neurons in the nucleus pontis oralis of the cat.

The present study was undertaken to explore the neuronal mechanisms of hypocretin actions on neurons in the nucleus pontis oralis (NPO), a nucleus which plays a key role in the generation of active (REM) sleep. Specifically, we sought to determine whether excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the laterodorsal tegmental nucleus (LDT) and spontaneous EPSPs in NPO neurons are modulated by hypocretin. Accordingly, recordings were obtained from NPO neurons in the cat in conjunction with the juxtacellular microinjection of hypocretin-1 onto intracellularly recorded cells. The application of hypocretin-1 significantly increased the mean amplitude of LDT-evoked EPSPs of NPO neurons. In addition, the frequency and the amplitude of spontaneous EPSPs in NPO neurons increased following hypocretin-1 administration. These data suggest that hypocretinergic processes in the NPO are capable of modulating the activity of NPO neurons that receive excitatory cholinergic inputs from neurons in the LDT.

Acetylcholine↗
PubMed1998

Rapid report: the reliability of excitatory synaptic transmission in slices of rat visual cortex in vitro is temperature dependent.

1. A total of twelve synaptic connections between pairs of pyramidal neurones in layer 2/3 of slices of rat visual cortex maintained in vitro was investigated using whole-cell voltage recordings under visual control. The connections varied widely in strength, with the mean peak amplitudes of the resulting excitatory postsynaptic potentials (EPSPs) ranging between approximately 40 microV and 2 mV at 23 degrees C. The smaller mean amplitudes included a substantial proportion of apparent failures of transmission. 2. The properties of these EPSPs were examined over a range of temperatures between 13 and 36 degrees C. All the connections became more reliable, in that they showed fewer apparent failures of transmission, and showed less trial-to-trial variability at the higher temperatures. These changes appeared to be due primarily to an increase in the mean number of transmitter quanta released per presynaptic action potential. 3. At 36 degrees C most connections were relatively reliable, with a mean failure rate of only 16 %. Five connections showed virtually no failures (1 % or fewer) at this temperature. 4. We conclude that quantal transmitter release is temperature dependent at these synapses, and that experiments performed at room temperature could lead to an exaggerated impression of the unreliability of transmission at central excitatory synapses.

Animals↗
PubMed2006

Acute behavioural stress facilitates long-term depression in temporoammonic-CA1 pathway.

Behavioural stress facilitates long-term depression in Schaffer collaterals-CA1 pathway, but it is unknown whether it influences long-term depression in temporoammonic fibres-CA1. Here, we report that low-frequency stimulation induced long-term depression and foot shock stress before slice preparation facilitated long-term depression in both pathways of young rat slices. When the field excitatory postsynaptic potentials were recorded by stimulating the two pathways alternately and low-frequency stimulation was given to the two pathways simultaneously, a reliable long-term depression was induced in Schaffer collaterals-CA1 but a reliable long-term potentiation took place in temporoammonic fibres-CA1. Interestingly, foot shock stress now enabled low-frequency stimulation to induce reliable long-term depressions in both pathways. These findings suggested that acute behavioural stress facilitated long-term depressions in both pathways and disrupted the interactions between pathways.

Animals↗
PubMed1964

ELECTROPHYSIOLOGY OF THE FETAL SPINAL CORD. II. INTERACTION AMONG PERIPHERAL INPUTS AND RECURRENT INHIBITION.

Interactions of peripheral inputs to the motoneuron of the kitten fetus as young as 3 weeks prenatal were studied by reflex discharge from the ventral root as well as by recording from single motoneurons. Facilitation was found between two synergists in fetuses 1 to 2 weeks before birth. Intracellular recording showed that the facilitation could be explained by summation of excitatory postsynaptic potentials. Inhibition was found between antagonists in the fetuses 2 to 3 weeks before birth and was accompanied by inhibitory postsynaptic potentials. Recurrent inhibition was very powerful in the fetal spinal cord as shown by large motoneuron hyperpolarization by antidromic stimulation. Cells presumed to be "Renshaw cells" and which responded to both ortho- and antidromic stimulation with repetitive firing were shown in the 2 weeks prenatal fetus. These results lead to the conclusion that there is considerable effective synaptic connection of afferent collaterals already established by the later stage of intrauterine life and that this may be achieved independently of external stimuli.

Axons↗
PubMed2000

Prenatal choline supplementation alters hippocampal N-methyl-D-aspartate receptor-mediated neurotransmission in adult rats.

Manipulation of dietary choline levels in pregnant rats has been shown to result in enduring alterations in memory and hippocampal function of the offspring, but the mechanisms underlying these effects remain unclear. Hippocampal slices were prepared from adult rats that were offspring of dams fed control, choline supplemented, or choline deficient diets on days 12-17 of gestation. N-methyl-D-aspartate (NMDA) receptor-mediated population excitatory postsynaptic potentials (pEPSPs) were pharmacologically isolated and evoked using electrical stimulus pulses applied to s. radiatum of area CA1. Evoked NMDA receptor-mediated pEPSPs were enhanced in slices from prenatally choline supplemented relative to controls in both male and female rats. The greatest differences occurred at the low end of the input-output curve, among responses that were less than 60% of maximal. These results are discussed in the context of previous behavioral and electrophysiological studies.

Age Factors↗
PubMed1998

A reexamination of the synaptic connection between neuron L7 of the abdominal ganglion and neurons of the branchial ganglion in Aplysia californica, A. kurodai and A. juliana.

The presence of a synaptic connection between neuron L7 of the abdominal ganglion and branchial ganglionic neurons (BGNs) was reexamined by means of electrophysiology and fluorescent microscopy using three Aplysia species. We succeeded in recording excitatory postsynaptic potentials produced in a BGN, which followed impulses of L7 one-to-one with a constant latency, even in A. californica as well as in A. kurodai and A. juliana. Dye-injection revealed that fine collaterals extended from a major branch of L7 to the branchial ganglion and arborized in neuropil of the ganglion. The results show that L7 in the three species has a dual function as a motor neuron and as an interneuron for the gill.

Animals↗