Refractoriness of sural nerve in humans

High-frequency stimulation of peripheral nerve bundles is frequently used in clinical tests and physiologic experiments to study presynaptic and postsynaptic effects. To understand the postsynaptic effects, it is important to ensure that each pulse in the train is equally effective in stimulating the presynaptic nerve bundle; however, the optimal interpulse interval (IPI) and the stimulus intensity at which each pulse is equally effective in stimulating the same number of axons are not known. The magnitude of the compound action potential produced by each pulse in a train was tested on the sural nerve of 4 healthy human subjects. The stimulus train (2-4 pulses) was applied to the sural nerve at the lateral malleolus, and neural responses were recorded from just below the knee. With 2-pulse trains, families of curves between IPIs (1-6 ms) and normalized amplitudes of the second response were plotted for different stimulus intensities. Visual inspection of the data showed that the curves fell into 2 groups: with stimulus intensities <2.5x perception threshold (Th), the test response appeared partially at longer IPIs, whereas with stimulus intensities >=3x Th, partial recovery of the test response was earlier. The interval for complete recovery was statistically the same for low- and high-intensity stimulation. With more than 2 pulses in a stimulus train (IPI = 5 ms), the amplitude of the compound action potential (CAP) was not affected significantly. These results are important in understanding both the presynaptic and postsynaptic responses when presynaptic axon bundles are stimulated at high frequencies.     

Characterization of the synaptic properties of olfactory bulb projections

The olfactory bulb directly projects to several diverse telencephalic structures, but, to date, few studies have investigated the physiological characteristics of most of these areas. As an initial step towards understanding the odor processing functions of these secondary olfactory structures, we recorded evoked field potentials in response to lateral olfactory tract stimulation in vivo in urethane-anesthetized Sprague-Dawley rats in the following brain structures: anterior olfactory nucleus, ventral and dorsal tenia tecta, olfactory tubercle, anterior and posterior piriform cortex, the anterior cortical nucleus of the amygdala, and lateral entorhinal cortex. Using paired-pulse stimulation with interpulse intervals of 25-1000 ms, we observed facilitation of the response to the second pulse in every structure examined, although the degree of facilitation varied among the target structures. Additionally, pulse train stimulation at three different frequencies (40, 10 and 2 Hz) produced facilitation of evoked field potentials that also varied among target structures. We discuss the potential utility of such short-term facilitation in olfactory processing.     

MPTP modulates hippocampal synaptic transmission and activity-dependent synaptic plasticity via dopamine receptors

Parkinson's disease (PD)-like symptoms and cognitive deficits are inducible by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Since cognitive abilities, including memory formations rely also on hippocampus, we set out to clarify the effects of MPTP on hippocampal physiology. We show that bath-application of MPTP (25?μM) to acute hippocampal slices enhanced AMPA receptor-mediated field excitatory postsynaptic potentials (AMPAr-fEPSPs) transiently, whereas N-methyl-D-aspartate (NMDA) receptor-mediated fEPSPs (NMDAr-fEPSPs) were facilitated persistently. The MPTP-mediated transient AMPAr-fEPSP facilitation was antagonized by the dopamine D2-like receptor antagonists, eticlopride (1?μM) and sulpiride (1 and 40?μM). In contrast, the persistent enhancement of NMDAr-fEPSPs was prevented by the dopamine D1-like receptor antagonist SCH23390 (10?μM). In addition, we show that MPTP decreased paired-pulse facilitation of fEPSPs and mEPSCs frequency. Regarding activity-dependent synaptic plasticity, 25?μM MPTP transformed short-term potentiation (STP) into a long-term potentiation (LTP) and caused a slow onset potentiation of a non-tetanized synaptic input after induction of LTP in a second synaptic input. This heterosynaptic slow onset potentiation required activation of dopamine D1-like and NMDA-receptors. We conclude that acute MPTP application affects basal synaptic transmission by modulation of presynaptic vesicle release and facilitates NMDAr-fEPSPs as well as activity-dependent homo- and heterosynaptic plasticity under participation of dopamine receptors.     

Role of reuniens nucleus projections to the medial prefrontal cortex and to the hippocampal pyramidal CA1 area in associative learning

We studied the interactions between short- and long-term plastic changes taking place during the acquisition of a classical eyeblink conditioning and following high-frequency stimulation (HFS) of the reuniens nucleus in behaving mice. Synaptic changes in strength were studied at the reuniens-medial prefrontal cortex (mPFC) and the reuniens-CA1 synapses. Input/output curves and a paired-pulse study enabled determining the functional capabilities of the two synapses and the optimal intensities to be applied at the reuniens nucleus during classical eyeblink conditioning and for HFS applied to the reuniens nucleus. Animals were conditioned using a trace paradigm, with a tone as conditioned stimulus (CS) and an electric shock to the trigeminal nerve as unconditioned stimulus (US). A single pulse was presented to the reuniens nucleus to evoke field EPSPs (fEPSPs) in mPFC and CA1 areas during the CS-US interval. No significant changes in synaptic strength were observed at the reuniens-mPFC and reuniens-CA1 synapses during the acquisition of eyelid conditioned responses (CRs). Two successive HFS sessions carried out during the first two conditioning days decreased the percentage of CRs, without evoking any long-term potentiation (LTP) at the recording sites. HFS of the reuniens nucleus also prevented the proper acquisition of an object discrimination task. A subsequent study revealed that HFS of the reuniens nucleus evoked a significant decrease of paired-pulse facilitation. In conclusion, reuniens nucleus projections to prefrontal and hippocampal circuits seem to participate in the acquisition of associative learning through a mechanism that does not required the development of LTP.     

Caspase-3 activity in the rat hippocampal slices reflects changes in synaptic plasticity

Considering the involvement of caspase-3 in neuronal plasticity, we studied caspase-3 activity in the rat hippocampal slices, and electrophysiological characteristics of extracellular responses to paired-pulse stimulation of Schaffer's collaterals in the CA1 subfield of hippocampus. Caspase-3 activity was measured after electrophysiological recording in each slice separately. Maximal caspase-3 activity was observed in the slices with low responsiveness to single afferent stimulation indicative of decreased efficacy of interneuronal interaction. This phenomenon is unrelated to depression of neuronal excitability since paired-pulse stimulation increases the synaptic efficacy to second stimulus thus restoring population spike amplitudes to normal values. In "damaged" slices with impaired spike generation up to disappearing spikes to both stimuli, caspase-3 activity was close to the normal level of the "healthy" slices. The activity of another proteinase, cathepsin B, was increased in the "damaged" slices, no correlation with the modifications of electrophysiological indices being detected. Our data suggest that high caspase-3 activity in hippocampal slices is involved in maintenance of synaptic plasticity but not necessarily related to apoptosis.     

Maternal infection and fever during late gestation are associated with altered synaptic transmission in the hippocampus of juvenile offspring rats

Prenatal exposure to infection is known to affect brain development and has been linked to increased risk for schizophrenia. The goal of this study was to investigate whether maternal infection and associated fever near term disrupts synaptic transmission in the hippocampus of the offspring. We used LPS to mimic bacterial infection and trigger the maternal inflammatory response in near-term rats. LPS was administered to rats on embryonic days 15 and 16 and hippocampal synaptic transmission was evaluated in the offspring on postnatal days 20-25. Only offspring from rats that showed a fever in response to LPS were tested. Schaffer collateral-evoked field excitatory postsynaptic potentials (fEPSPs) and fiber volleys in CA1 of hippocampal slices appeared smaller in offspring from the LPS group compared with controls, but, when the fEPSPs were normalized to the amplitude of fiber volleys, they were larger in the LPS group. In addition, intrinsic excitability of CA1 pyramidal neurons was heightened, as antidromic field responses in the LPS group were greater than those from control. Short-, but not long-term plasticity was impaired since paired-pulse facilitation of the fEPSP was attenuated in the LPS group, whereas no differences in long-term potentiation were noted. These results suggest that LPS-induced inflammation during pregnancy produces in the offspring a reduction in presynaptic input to CA1 with compensatory enhancements in postsynaptic glutamatergic response and pyramidal cell excitability. Neurodevelopmental disruption triggered by prenatal infection can have profound effects on hippocampal synaptic transmission, likely contributing to the memory and cognitive deficits observed in schizophrenia.     

A tale of two stories: astrocyte regulation of synaptic depression and facilitation

Short-term presynaptic plasticity designates variations of the amplitude of synaptic information transfer whereby the amount of neurotransmitter released upon presynaptic stimulation changes over seconds as a function of the neuronal firing activity. While a consensus has emerged that the resulting decrease (depression) and/or increase (facilitation) of the synapse strength are crucial to neuronal computations, their modes of expression in vivo remain unclear. Recent experimental studies have reported that glial cells, particularly astrocytes in the hippocampus, are able to modulate short-term plasticity but the mechanism of such a modulation is poorly understood. Here, we investigate the characteristics of short-term plasticity modulation by astrocytes using a biophysically realistic computational model. Mean-field analysis of the model, supported by intensive numerical simulations, unravels that astrocytes may mediate counterintuitive effects. Depending on the expressed presynaptic signaling pathways, astrocytes may globally inhibit or potentiate the synapse: the amount of released neurotransmitter in the presence of the astrocyte is transiently smaller or larger than in its absence. But this global effect usually coexists with the opposite local effect on paired pulses: with release-decreasing astrocytes most paired pulses become facilitated, namely the amount of neurotransmitter released upon spike i+1 is larger than that at spike i, while paired-pulse depression becomes prominent under release-increasing astrocytes. Moreover, we show that the frequency of astrocytic intracellular Ca(2+) oscillations controls the effects of the astrocyte on short-term synaptic plasticity. Our model explains several experimental observations yet unsolved, and uncovers astrocytic gliotransmission as a possible transient switch between short-term paired-pulse depression and facilitation. This possibility has deep implications on the processing of neuronal spikes and resulting information transfer at synapses.     

Prenatal experience and postnatal development of the rat hippocampus: sleep deprivation of pregnant rats

The effects of sleep deprivation in pregnancy on the development of hippocampal function of the offspring have been investigated. For this purpose we compared electrophysiological characteristics in the hippocampal slices of 15-20-old-day rats of the control and two experimental groups. In the first experimental group the pups were taken from mother for weighting three times during the first postnatal week and then weekly. Another experimental group was brought up without handling. We found that CA1 population spikes developed to significantly less amplitude in experimental groups of rat pups. This phenomenon was observed at higher intensity of monosynaptic activation, although near-threshold stimuli didn't reveal any differences among groups. However, under paired-pulse stimulation (70 ms inter-pulse interval) small amplitudes in the hippocampal slices of experimental animals could facilitate up to control value, and second in pair responses didn't differ from corresponding control. Our data doesn't confirm the hypothesis about decreased connectivity in the hippocampus of experimental rats, but the efficacy of CA3-CA1 inputs seems to be lower. Besides excitatory transmission, the effectiveness of inhibition of paired-pulse facilitation at 15 ms inter-pulse interval was also significantly decreased. The observed effects of prenatal influences seem to develop under postnatal experience. We observed significant trend to more pronounced modifications upon age especially in the case of early handling and testing.     

Numerical modelling of plasticity induced by transcranial magnetic stimulation

We use neural field theory and spike-timing dependent plasticity to make a simple but biophysically reasonable model of long-term plasticity changes in the cortex due to transcranial magnetic stimulation (TMS). We show how common TMS protocols can be captured and studied within existing neural field theory. Specifically, we look at repetitive TMS protocols such as theta burst stimulation and paired-pulse protocols. Continuous repetitive protocols result mostly in depression, but intermittent repetitive protocols in potentiation. A paired pulse protocol results in depression at short ( < ～ 10 ms) and long ( > ～ 100 ms) interstimulus intervals, but potentiation for mid-range intervals. The model is sensitive to the choice of neural populations that are driven by the TMS pulses, and to the parameters that describe plasticity, which may aid interpretation of the high variability in existing experimental results. Driving excitatory populations results in greater plasticity changes than driving inhibitory populations. Modelling also shows the merit in optimizing a TMS protocol based on an individual’s electroencephalogram. Moreover, the model can be used to make predictions about protocols that may lead to improvements in repetitive TMS outcomes.     

Taurine regulation of short term synaptic plasticity in fragile X mice

Background

Fragile X Syndrome is the most common known genetic cause of autism. The Fmr1-KO mouse, lacks the fragile X mental retardation protein (FMRP), and is used as a model of the syndrome. The core behavioral deficits of autism may be conceptualized either as excessive adherence to patterns as seen in repetitive actions and aberrant language, or as insensitivity to subtle but socially important changes in patterns. The hippocampus receives information from the entorhinal cortex and plays a crucial role in the processing of patterned information. To gain more insight into the physiological function of FMRP and the neuronal mechanisms underlying fragile X syndrome, we examined the electrophysiological response of the hippocampus to pair pulse stimulation as a measure of patterned information processing and how it is affected in the Fmr1-KO mouse.

Methods

In this study, we used paired-pulse stimulation of the afferent perforant path and recorded from the CA1 region of the hippocampus. Two-month-old FVB/NJ male mice and age-matched Fmr1-KO mice were used in this study. Hippocampal slices were prepared, equilibrated in artificial cerebrospinal fluid (aCSF), and excitatory post synaptic potentials (EPSPs) measured by stimulating the perforant path of the dentate gyrus (DG) while recording from the molecular layer of CA1. Stimulation occurred by setting current and pulse width to evoke a fixed percentage of maximal EPSP amplitude. This stimulation paradigm allowed us to examine the processing capabilities of the hippocampus as a function of increasing interstimulus intervals (ISI) and how taurine, a GABA_A receptor agonist, affects such information processing.

Results

We found that hippocampal slices from wild type (WT) showed pair-pulse facilitation at ISI of 100-300 ms whereas slices from Fmr1-KO brains showed a consistent pair-pulse depression at a comparable ISI. Addition of 10 μM taurine to WT slices resulted in a drastic decrease of the peak response to the second stimulus, resulting in an initial depression at 100 ms ISI followed by potentiation at higher ISI (150 ms and above). In the presence of taurine, the amplitude of the second response remained significantly lower than in its absence. Fmr1-KO mice however, were completely insensitive to taurine application and pair-pulse stimulation always resulted in a depression of the response to the second stimulus.

Conclusions

Previously we reported that Fmr1-KO mice have reduced beta subunits of the GABA_A receptors. We also showed as well as others that taurine acts as an agonist or a modulator for GABA_A receptors. Therefore, the insensitivity of Fmr1-KO slices to taurine application could be due to the reduced binding sites on the GABA_A receptors in the Fmr1-KO mice.

     

Excitability cycles of direct cortical responses during elaboration of conditioned defense reflexes in dogs]

Direct cortical responses (DCRs) to paired stimuli were studied in chronic experiments in dogs during elaboration of classical and instrumental defensive conditioned reflexes. The DCRs were recorded with 20 to 250 ms intervals between stimuli. Paired and single electrical stimulations of the middle suprasylvian gyrus given with a frequency of one per second were used as conditioned stimuli and were reinforced in a similar way. During electrical cutaneous stimulation of the dog's paw and to an even greater extent during isolated action of the conditioned stimulus the initial negativity of the testing DCR became shorter and the degree of its depression diminished. In the case of a following period of facilitation, its degree became greater. It was higher at a distance of 4 to 5 mm from the point of stimulation than at a distance of 2 to 3 mm. During isolated action of the conditioned stimulus, the degree of facilitation was higher than at the period of the possible action of the unconditioned stimulus. The greatest shorterning of the DCR excitability cycle was observed immediately before and during the conditioned lifting of the dog's paw. Excitability cycles of DCR, and possibly of other evoked potentials as well, are a more sensitive indicator of the function state of the cerebral cortex than responses to single stimuli. For this reason it appears promising to use them in studying conditioned reflexes.     

Differential expression of posttetanic potentiation and retrograde signaling mediate target-dependent short-term synaptic plasticity

Short-term synaptic plasticity influences how presynaptic spike patterns control the firing of postsynaptic targets. Here we investigated whether specific mechanisms of short-term plasticity are regulated in a target-dependent manner by comparing synapses made by cerebellar granule cell parallel fibers onto Golgi cells (PF-->GC synapse) and Purkinje cells (PF-->PC synapse). Both synapses exhibited similar facilitation, suggesting that any differential short-term plasticity does not reflect differences in the initial release probability. PF-->PC synapses were highly sensitive to stimulus bursts, which could result in either depression of subsequent responses, mediated by endocannabinoid-dependent retrograde signaling, or enhancement of responses through posttetanic potentiation (PTP). In contrast, stimulus bursts had remarkably little effect on the strength of PF-->GC synapses. Unlike PCs, GCs were unable to regulate their PF synapses by releasing endocannabinoids. Moreover, PTP was reduced at the PF-->GC synapse compared to the PF-->PC synapse. Thus, the target-dependence of PF synapses arises from the differential expression of both retrograde signaling and PTP.     

低铅暴露对大鼠海马突触可塑性范围的影响

长时程增强(LTP)和长时程抑制(LTD),作为突触可塑性变化的两种主要形式,被认为是学习记忆的可能机制.突触可塑性范围可以定量的表征突触可塑性的变化.应用在体电生理技术,在同一只动物上记录LTP和LTD,研究了发育过程中慢性铅暴露对大鼠海马齿状回颗粒细胞突触可塑性范围和双脉冲易化的影响.对照组的LTP、LTD的幅度分别是187.9±6.2%(n＝7),85.2±1.6%(n＝7),而铅处理组分别为140.5±1.2%(n＝7),102.8±3.8%(n＝7).与对照组相比,铅处理组的LTP的幅度降低了47.4%,LTD的诱导几乎完全被铅损伤.先诱导出LTP后再通过低频刺激则可以在铅处理组诱导出LTD(81.5±2.2%(n＝7)),但远远小于对照组(66.8±4.3%(n＝7)).对照组突触可塑性范围是103.1±11.5%(n＝7),是铅处理组突触可塑性范围(37.7±9.6%(n＝7))的2.7倍.在对照组,双脉冲易化反应是从脉冲间隔20ms时开始,而铅处理组则是从50ms开始.当脉冲间隔为70ms时,两组的双脉冲易化幅度均达到最大值,但易化的强度有显著的差异,分别为211.6±32.2%(n＝7),11.1±26.9%(n＝7).结果表明铅显著地抑制了大鼠海马齿状回颗粒细胞的双脉冲易化效应,降低了双脉冲易化的间隔范围和突触可塑性范围.这可能是铅损伤学习记忆功能的机制之一.     

Nonlinear cross-frequency interactions in primary auditory cortex spectrotemporal receptive fields: a Wiener–Volterra analysis

The effects of nonlinear interactions between different sound frequencies on the responses of neurons in primary auditory cortex (AI) have only been investigated using two-tone paradigms. Here we stimulated with relatively dense, Poisson-distributed trains of tone pips (with frequency ranges spanning five octaves, 16 frequencies /octave, and mean rates of 20 or 120 pips /s), and examined within-frequency (or auto-frequency) and cross-frequency interactions in three types of AI unit responses by computing second-order “Poisson-Wiener” auto- and cross-kernels. Units were classified on the basis of their spectrotemporal receptive fields (STRFs) as “double-peaked”, “single-peaked” or “peak-valley”. Second-order interactions were investigated between the two bands of excitatory frequencies on double-peaked STRFs, between an excitatory band and various non-excitatory bands on single-peaked STRFs, and between an excitatory band and an inhibitory sideband on peak-valley STRFs. We found that auto-frequency interactions (i.e., those within a single excitatory band) were always characterized by a strong depression of (first-order) excitation that decayed with the interstimulus lag up to ～200 ms. That depression was weaker in cross-frequency compared to auto-frequency interactions for ～25% of dual-peaked STRFs, evidence of “combination sensitivity” for the two bands. Non-excitatory and inhibitory frequencies (on single-peaked and peak-valley STRFs, respectively) typically weakly depressed the excitatory response at short interstimulus lags (<50 ms), but weakly facilitated it at longer lags (～50–200 ms). Both the depression and especially the facilitation were stronger for interactions with inhibitory frequencies rather than just non-excitatory ones. Finally, facilitation in single-peaked and peak-valley units decreased with increasing stimulus density. Our results indicate that the strong combination sensitivity and cross-frequency facilitation suggested by previous two-tone-paradigm studies are much less pronounced when using more temporally-dense stimuli.     

The effect of vibrissa deprivation pattern on the form of plasticity induced in rat barrel cortex

Plasticity was induced in the barrel cortex of adolescent rats by depriving every second vibrissa on the contralateral vibrissa pad.This produced a chessboard pattern of barrels in the cortex where each barrel receiving its principal input from a spared vibrissa was surrounded by barrels for which the principal vibrissa had been deprived and conversely, each barrel receiving its principal input from a deprived vibrissa was surrounded by barrels for which the principal vibrissa had been spared. After 7 days' deprivation, responses to the regrown vibrissae were depressed in layers II/III (49% of control levels) and IV (60%). Depression was far greater than that seen with "all vibrissa" deprivation, suggesting that activity in the spared vibrissae accentuated the depression of the deprived vibrissae. Depression was not due to subcortical changes as thalamic Ventral Posterior Medial (VPM) responses to deprived vibrissa were unchanged. The short latency responses in layer IV (5-7 ms) were unaffected by deprivation, but the number of cells responding at intermediate latencies (8-13 ms) was markedly reduced (to 66% of control). Potentiation of the spared vibrissa response was substantial in the near side of the neighbouring barrel (2.2-fold increase in layers II/III, 2.9-fold in layer IV) but had not spread to the far side after 7 days' deprivation. Sparing multiple vibrissae may increase the rate of potentiation since 7 days is insufficient time for potentiation in single vibrissa spared animals. Potentiation was not due to subcortical changes as thalamic VPm responses to the spared vibrissa were normal. However, in the spared barrel the response latency decreased by 1-2 ms. Only the cells responding at short latency exhibited potentiated responses (39% increase) suggesting that some thalamocortical plasticity is still possible at P28-35. These results show that chessboard pattern deprivation is capable of inducing substantial plasticity over a wide area of barrel cortex. All the major forms of plasticity seen with other vibrissa deprivation patterns were present, although no other single deprivation pattern studied so far causes the complete repertoire seen with chessboard deprivation.     

Hyperexcitability and changes in activities of Ca2+/calmodulin-dependent kinase II and mitogen-activated protein kinase in the hippocampus of rats exposed to 1-bromopropane

Chronic inhalation of 1-bromopropane (1-BP), a substitute of ozone-depleting chlorofluorocarbons, has been suspected of having central neurotoxicity (Clinical Neurology and Neurosurgery 101 (1999) 199; Journal of Occupational Health 44 (2002) 1) for humans. In animal experiments, 1-BP inhalation (1500 ppm) caused hyperexcitability in the CA1 and the dentate gyrus (DG) [Journal of Occupational Health 42 (2000) 149, Journal of Occupational Health 44 (2002) 156]. We studied whether the hyperexcitability is associated with changes of Ca2+/calmodulin-dependent kinase II (CaMKII), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC). Male Wistar rats were exposed to 1-BP for 6 hours in a day in an exposure chamber with a concentration of 700 ppm for 8 weeks. After the inhalation, paired-pulse ratios of field excitatory postsynaptic potentials and population spikes (PSs) were analyzed in the CA1 and DG of hippocampal slices. Control rats were then given fresh air in the inhalation chamber. Semiquantitative immunoblotting analyses of protein kinases using antibodies against active and conventional protein kinases were done using the whole hippocampus. A paired-pulse ratio of PS was increased at the 5 ms interpulse interval in the CA1 and at the 10-20 ms interpulse intervals in the DG. The amount of active MAPK and total amount of CaMKIIalpha and beta were significantly increased by 28, 29, and 46% compared to control, respectively, without any change in PKC activity. In contrast, the amount of active CaMKIIbeta was decreased to 78%. These results suggest that modifications of intracellular signaling cascades are associated with hyperexcitability that occurred in the hippocampal formation of rats exposed to the chronic inhalation of 1-BP.     

Lentiviral Expression of Rabies Virus Glycoprotein in the Rat Hippocampus Strengthens Synaptic Plasticity

Rabies virus (RABV) is a neurotropic virus exclusively infecting neurons in the central nervous system. RABV encodes five proteins. Among them, the viral glycoprotein (RVG) plays a key role in viral entry into neurons and rabies pathogenesis. It was shown that the nature of the C-terminus of the RABV G protein, which possesses a PDZ-binding motif (PBM), modulates the virulence of the RABV strain. The neuronal protein partners recruited by this PBM may alter host cell function. This study was conducted to investigate the effect of RVG on synaptic function in the hippocampal dentate gyrus (DG) of rat. Two μl (10⁸ T.U./ml) of the lentiviral vector containing RVG gene was injected into the DG of rat hippocampus. After 2 weeks, the rat’s brain was cross-sectioned and RVG-expressing cells were detected by fluorescent microscopy. Hippocampal synaptic activity of the infected rats was then examined by recording the local field potentials from DG after stimulation of the perforant pathway. Short-term synaptic plasticity was also assessed by double pulse stimulation. Expression of RVG in DG increased long-term potentiation population spikes (LTP-PS), whereas no facilitation of LTP-PS was found in neurons expressing δRVG (deleted PBM). Furthermore, RVG and δRVG strengthened paired-pulse facilitation. Heterosynaptic long-term depression (LTD) in the DG was significantly blocked in RVG-expressing group compared to the control group. This blockade was dependent to PBM motif as rats expressing δRVG in the DG-expressed LTD comparable to the RVG group. Our data demonstrate that RVG expression facilitates both short- and long-term synaptic plasticity in the DG indicating that it may involve both pre- and postsynaptic mechanisms to alter synaptic function. Further studies are needed to elucidate the underlying mechanisms.

     

Mechanisms of neurotransmitter release facilitation in strontium solutions

Mechanisms of neurotransmitter release facilitation were studied using electrophysiological recording of end-plate currents (EPC) and nerve ending (NE) responses after substitution of extracellular Ca ions with Sr ions at the frog neuromuscular junction. The solutions with 0.5 mM concentration of Ca ions (calcium solution) or 1 mM concentration of Sr ions (strontium solution) were used where baseline neurotransmitter release (at low-frequency stimulation) is equal. Decay of paired-pulse facilitation of EPC at calcium solutions with increase of interpulse interval from 5 to 500 ms was well described by three-exponential function consisting of early, first and second components. Facilitation at strontium solutions was significantly diminished due mainly to decrease of early and first components. At the same time, EPC facilitation with rhythmic stimulation (10 or 50 imp/s) at strontium solutions was significantly increased. Also more pronounced decrease of NE response 3rd phase, reflecting potassium currents was detected under rhythmic stimulation of 50 imp/s at strontium solutions comparing to calcium solutions. It was concluded that facilitation sites underlying first and early components had lower affinity to Sr ions than to Ca ions. The enhancement of frequency facilitation at strontium solutions is mediated by two mechanisms: more pronounced broadening of NE action potential and increase of bivalent cation influx due to feebly marked activation of Ca(2+)-dependent potassium current by Sr ions, and slower dynamics of Sr(2+) removal from NE axoplasm comparing to Ca(2+).     

Automatic Realistic Real Time Stimulation/Recording in Weakly Electric Fish: Long Time Behavior Characterization in Freely Swimming Fish and Stimuli Discrimination

Weakly electric fish are unique model systems in neuroethology, that allow experimentalists to non-invasively, access, central nervous system generated spatio-temporal electric patterns of pulses with roles in at least 2 complex and incompletely understood abilities: electrocommunication and electrolocation. Pulse-type electric fish alter their inter pulse intervals (IPIs) according to different behavioral contexts as aggression, hiding and mating. Nevertheless, only a few behavioral studies comparing the influence of different stimuli IPIs in the fish electric response have been conducted. We developed an apparatus that allows real time automatic realistic stimulation and simultaneous recording of electric pulses in freely moving Gymnotus carapo for several days. We detected and recorded pulse timestamps independently of the fish’s position for days. A stimulus fish was mimicked by a dipole electrode that reproduced the voltage time series of real conspecific according to previously recorded timestamp sequences. We characterized fish behavior and the eletrocommunication in 2 conditions: stimulated by IPIs pre-recorded from other fish and random IPI ones. All stimuli pulses had the exact Gymontus carapo waveform. All fish presented a surprisingly long transient exploratory behavior (more than 8 h) when exposed to a new environment in the absence of electrical stimuli. Further, we also show that fish are able to discriminate between real and random stimuli distributions by changing several characteristics of their IPI distribution.     

Impaired learning with enhanced hippocampal long-term potentiation in PTPdelta-deficient mice

Protein tyrosine phosphatase delta (PTPdelta) is a receptor-type PTP expressed in the specialized regions of the brain including the hippocampal CA2 and CA3, B lymphocytes and thymic medulla. To elucidate the physiological roles of PTPdelta, PTPdelta-deficient mice were produced by gene targeting. It was found that PTPdelta-deficient mice were semi-lethal due to insufficient food intake. They also exhibited learning impairment in the Morris water maze, reinforced T-maze and radial arm maze tasks. Interestingly, although the histology of the hippocampus appeared normal, the magnitudes of long-term potentiation (LTP) induced at hippocampal CA1 and CA3 synapses were significantly enhanced in PTPdelta-deficient mice, with augmented paired-pulse facilitation in the CA1 region. Thus, it was shown that PTPdelta plays important roles in regulating hippocampal LTP and learning processes, and that hippocampal LTP does not necessarily positively correlate with spatial learning ability. To our knowledge, this is the first report of a specific PTP involved in the regulation of synaptic plasticity or in the processes regulating learning and memory.