Potentiation of excitatory postsynaptic potentials during and after repetitive stimulation in thin hippocampal sections

Summary Excitatory postsynaptic potentials (EPSPs) elicited by mossy fiber stimulation were recorded intracellularly from neurons in the CA₃ region in thin hippocampal sections in vitro and potentiation of the EPSPs was examined during and after repetitive stimulation. Inhibitory postsynaptic potentials (IPSPs) and seizure discharges were blocked by bicuculline and high concentrations of Mg²⁺. When two shocks were applied at short intervals, the second EPSP was markedly potentiated. This potentiation declined exponentially with a time-constant of about 180 ms and was unaffected by changes in ambient temperature. The amount of potentiation during a pulse train was explained by summation of potentiation by individual pulses. Post tetanic potentiation lasted longer in media containing Ca²⁺ at higher concentrations and Mg²⁺ at lower concentrations. At high Ca²⁺ concentrations, tetanic stimulation induced long-term potentiation which was occasionally preceded by a long-lasting suppression. Tetanus to a bundle of mossy fibers potentiated EPSPs elicited by stimulation of a separate bundle of mossy fibers (heterosynaptic potentiation) but did not augment EPSPs elicited by fimbrial stimulation.     

Intracellular correlates of spatial memory acquisition in hippocampal slices: long-term disinhibition of CA1 pyramidal cells

Despite many advances in our understanding of synaptic models of memory such as long-term potentiation and depression, cellular mechanisms that correlate with and may underlie behavioral learning and memory have not yet been conclusively determined. We used multiple intracellular recordings to study learning-specific modifications of intrinsic membrane and synaptic responses of the CA1 pyramidal cells (PCs) in slices of the rat dorsal hippocampus prepared at different stages of the Morris water maze (WM) task acquisition. Schaffer collateral stimulation evoked complex postsynaptic potentials (PSP) consisting of the excitatory and inhibitory postsynaptic potentials (EPSP and IPSP, respectively). After rats had learned the WM task, our major learning-specific findings included reduction of the mean peak amplitude of the IPSPs, delays in the mean peak latencies of the EPSPs and IPSPs, and correlation of the depolarizing-shifted IPSP reversal potentials and reduced IPSP-evoked membrane conductance. In addition, detailed isochronal analyses revealed that amplitudes of both early and late IPSP phases were reduced in a subset of the CA1 PCs after WM training was completed. These reduced IPSPs were significantly correlated with decreased IPSP conductance and with depolarizing-shifted IPSP reversal potentials. Input-output relations and initial rising slopes of the EPSP phase did not indicate learning-related facilitation as compared with the swim and na?ve controls. Another subset of WM-trained CA1 PCs had enhanced amplitudes of action potentials but no learning-specific synaptic changes. There were no WM training-specific modifications of other intrinsic membrane properties. These data suggest that long-term disinhibition in a subset of CA1 PCs may facilitate cell discharges that represent and record the spatial location of a hidden platform in a Morris WM.     

Postsynaptic membrane shifts during frequency potentiation of the hippocampal EPSP

1. In some classes of central neurons, repetitive synaptic stimulation induces substantial changes in the postsynaptic membrane, in conjunction with robust frequency potentiation of the excitatory postsynaptic potential (EPSP). However, the nature and time course of these postsynaptic membrane shifts, or their possible contributions to EPSP frequency potentiation (e.g., by altering driving force or current pathways), have not been examined extensively. We therefore studied the simultaneous patterns of change in composite EPSP amplitude, postsynaptic input resistance (Rin), and postsynaptic membrane potential during a 4-min train of 10-Hz monosynaptic stimulation in CA1 neurons of hippocampal slices. Slices were maintained in media containing either control (4 mM) or high (6.5 mM) concentrations of K+. 2. Potentiation of the EPSP, hyperpolarization of the membrane, and a decline of Rin, all developed rapidly during 10-Hz synaptic stimulation; these responses reached maximal levels by 5-15 s of the stimulation train. In most cells, a membrane depolarization phase occurred between 15 and 45 s of stimulation, followed by rehyperpolarization by 1 min of stimulation. During the depolarization phase, both EPSP potentiation and the decline in Rin remained near maximal. No significant differences were seen as a function of K+ concentrations. 3. These results show that hyperpolarization is not invariably associated temporally with EPSP frequency potentiation. Moreover, if driving force and membrane conductance changes are assumed to be approximately similar in large dendrites and soma, then the increase in driving force due to membrane hyperpolarization was not sufficient to account for the three- and fourfold increases in EPSP amplitude seen during frequency potentiation. Further, based on similar assumptions and on dendritic models of EPSP attenuation, the decline in Rin should reduce EPSP amplitude at the dendritic synaptic site and, to a proportionately greater extent, at the soma. 4. Studies in which the membrane was hyperpolarized with injected current to approximately the IPSP reversal potential, or in which bicuculline methiodide was applied to the slices, indicated that depression of the IPSP by repetitive stimulation did not account for frequency potentiation of EPSP amplitude. 5. These data are therefore consistent with the conclusion that the frequency potentiation of composite EPSPs in central neurons depends on presynaptic mechanisms, rather than on generalized postsynaptic changes. However, our findings do not rule out localized postsynaptic changes in receptors or spines as possible contributing factors.(ABSTRACT TRUNCATED AT 400 WORDS)     

Use-dependent depression of IPSPs in rat hippocampal pyramidal cells in vitro

We have used intracellular recording techniques to study the use-dependence of evoked inhibitory postsynaptic potentials (IPSPs) in rat CA1 hippocampal pyramidal cells. We determined reversal potentials and conductance changes associated with IPSPs and responses to directly applied gamma-aminobutyric acid (GABA). The IPSP depression could be seen after a single conditioning stimulus. This depression appeared to be due primarily to a 50% decrease in IPSP conductance (gIPSP). Trains of stimulating pulses (50 pulses at 5 or 10 Hz) produced more pronounced effects than a single conditioning pulse. Suprathreshold repetitive stimulation of stratum radiatum (SR) produced epileptiform burst firing and greater depression of IPSPs than did alvear (ALV) or subthreshold SR stimulation. During suprathreshold SR stimulation the IPSP was nearly abolished and the membrane potential could become less negative than the resting potential. A masking effect of facilitated depolarizing potentials on IPSPs was unlikely since IPSPs accompanied by little or no depolarizing potential were also depressed by SR trains. The 75% reduction in IPSP conductance found after repetitive stimulation confirmed that an overlapping conductance was not responsible for the depression of the IPSP. The GABA-induced conductance increase was not depressed by identical trains. Trains of stimulation induced depolarizing shifts in equilibrium potentials for the IPSP (EIPSP) and GABA (EGABA) of approximately 10 mV. These shifts were always greater after SR trains than after ALV trains. Simultaneous recordings of membrane potential and extracellular potassium concentration ([K+]o) with K+-sensitive microelectrodes revealed a direct correlation between the two during a stimulus train. Membrane potential depolarized as much as 18 mV from the peak of the IPSP and [K+]o could increase to a maximum of 10 mM during some trains. A depressant effect (of approximately 50%) of K+ on IPSPs was demonstrated by brief pressure ejection of K+ near the soma. We conclude that repetitive stimulation depresses gIPSP and shifts EIPSP in the depolarizing direction. Whereas gIPSP began to decline after a single conditioning pulse, the additional depression of IPSPs produced by stimulus trains was due in large part to shifts in EIPSP. Depression of gIPSP was not due to desensitization or block of ionic conductances, since gGABA was not reduced. The EIPSP may change as a result of increases in [K+]o.     

Quantitative studies of intracellular postsynaptic potentials in the lateral geniculate nucleus of the cat with respect to optic tract stimulus response latencies

Summary LGN cells were intracellularly recorded with glass micropipettes. Electrical stimuli of different amplitude and frequency were applied to the optic tract close to the optic chiasm. The cells were classified according to stimulus response latencies of action potentials as belonging to class I (1.0–1.6 msec) or class II (1.7–3.0 msec).Class I EPSPs had shorter latencies (1.0–1.5 msec), durations (4–12 msec), rise times to peak (0.5–1.4 msec), and decay times (3.0–8.5 msec); the synaptic transmission time was on the average 0.41 msec. Class II EPSPs (1.6–2.6 msec latency) had longer durations (10–30 msec), rise times (1.6–3.7 msec), and decay times (9.0–25 msec); the synaptic transmission time was on the average 0.67 msec.With repetitive stimulation the EPSPs of latency class I revealed almost no stimulus frequency dependence between 1 and 120 Hz, while class II EPSPs decreased in amplitude between 30 and 70% with increasing frequency. Comparable temporal summation of excitation occurred in cells of both latency classes. Negative serial correlation coefficients of first order were found for consecutive EPSP amplitudes of all cells recorded for sufficient periods of time.The IPSPs were subdivided into two groups according to their optic tract response latency. Group 1 IPSPs had shorter latencies (2.0–2.6 msec), durations (15–50 msec), and times from the onset to maximal hyperpolarization (2.4–4.2 msec) than group 2 IPSPs (3.0–4.8 msec latency, 40–100 msec duration, 2.7–7.5 msec time from onset to extremum).The group 2 IPSPs decreased in amplitude by about 90% when the stimulus frequency was increased from 1 to 50 Hz, while the group 1 IPSPs displayed a comparable decrease in the frequency range between 50 and 120 Hz. Effective temporal summation was found in group 2 IPSPs in the frequency range below 70 Hz, and in group 1 IPSPs at stimulus frequencies between 70 and 120 Hz.The EPSP peak latencies and the latencies to the minimum of IPSPs proved to be invariant with respect to PSP amplitude and stimulus frequency in individual cells. The latencies to the extrema of EPSPs and IPSPs as well as the amplitude values were symmetrically distributed.     

Statistical analysis of long-term potentiation of large excitatory postsynaptic potentials recorded in guinea pig hippocampal slices: binomial model

Summary Excitatory postsynaptic potentials (EPSPs) were recorded in guinea pig hippocampal slices (area CA1) from 15 neurones after stimulation of stratum radiatum (str. rad.) and stratum oriens. EPSP amplitudes increased in 8 neurones (10 post-tetanic regions) recorded 15 to 45 min after tetanic stimulation of str. rad. The increase was considered to represent long-term potentiation (LTP). Quantal analysis was performed by two methods assuming binomial statistics: the histogram method using deconvolution of noise and the variance method. According to both methods, LTP was associated with an increase in mean quantal content (m) which correlated with LTP magnitude. A statistically significant increase in quantal size (v) was found only by the histogram method and the increase was not correlated with LTP magnitude. A separate analysis of EPSPs with small LTP magnitude demonstrated that with the histogram method only v was increased but not m. A smaller increase in m for the pooled data of both methods did not correlate with LTP magnitude for this EPSP subset. The increase in m for the whole EPSP set corresponds to previous results on the quantal analysis of LTP in in vivo preparations and favours a presynaptic location of major mechanisms underlying LTP maintenance. The increase in v indicates the existence of another mechanism responsible for the maintenance of a small part of LTP. This mechanism might involve either pre- or postsynaptic changes or both.     

Heterosynaptic facilitation and post-tetanic potentiation in Aplysia nervous system

1. Heterosynaptic facilitation was defined as an increase of amplitude of a test excitatory post-synaptic potential (EPSP) after the activation of a pathway (heterosynaptic pathway) different from that which produced the test EPSP. This phenomenon has been studied in Aplysia central nervous system under conditions which excluded the participation of post-tetanic potentiation.2. A unitary test was produced in the left and right giant cells, by indirect stimulation of an interneurone located in the peri-oesophageal ring.3. During heterosynaptic stimulation, orthodromic and antidromic activation of the test interneurone was prevented by (1) isolating the synaptic afferent region of the test interneurone from the tested synapse on the right giant cell by a sucrose block applied on the left pleurovisceral connective, and (2) using physiological stimulation of a piece of skin as a heterosynaptic stimulus.Under these conditions which prevented any firing in the test interneurone, heterosynaptic facilitation is observed as a 200% increase of amplitude of the test EPSP in the right cell which lasted more than 15 min.When instead of the physiological stimulus a supramaximal electrical stimulation of the nerves afferent to the abdominal ganglion was used, the increase of amplitude of the test EPSP could reach as much as 500% of its original amplitude. The effectiveness of such heterosynaptic stimulus was smaller when it was applied in the absence of a block of the left pleuro-visceral connective.4. It was possible to produce heterosynaptic facilitation when the preparation was cooled to 7-9 degrees C or if Li(+) replaced Na(+) in the medium. Both of these changes suppressed post-tetanic potentiation.5. It was concluded that heterosynaptic facilitation is a phenomenon different from post-tetanic potentiation. Heterosynaptic facilitation is similar to heterosynaptic inhibition seen in other cells in the same preparation, except for the polarity of action. Both phenomena seem to result from comparable mechanisms, probably acting on the quantity of transmitter released.     

Selective inhibition of homosynaptic depression in a tetanized pathway by an adenosine A1 blocker in the CA1 region of rat hippocampal slice.

The involvement of adenosine A1 receptors in post-tetanic depression (PTD) of CA1, induced by 5 Hz, 20 s stimulation to the Schaffer collateral/commissural fibers was studied in the rat hippocampal slice. The tetanic stimulation induced post-tetanic depression (PTD) lasting for 5-10 min in the excitatory postsynaptic potentials (EPSP) and the population spike (PS) of the tetanized pathway (homosynaptic PTD), and of a non-tetanized pathway (heterosynaptic PTD). 8-Cyclopentyltheophylline (an adenosine A1 antagonist) blocked the induction of homosynaptic PTD, but not of heterosynaptic PTD. These results indicate that adenosine released during tetanic stimulation acts on the A1 receptor to induce the homosynaptic PTD.     

Induction of long-term potentiation without participation of N-methyl-D-aspartate receptors in kitten visual cortex.

1. Intracellular recording was made from layer II-III cells in slice preparations of kitten (30-40 days old) visual cortex. Low-frequency (0.1 Hz) stimulation of white matter (WM) usually evoked an excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP). The postsynaptic potentials (PSPs) showed strong dependence on stimulus frequency. Early component of EPSP and IPSP evoked by weak stimulation both decreased monotonically at frequencies greater than 0.5-1 Hz. Strong stimulation similarly depressed the early EPSP at higher frequencies (greater than 2 Hz) and replaced the IPSP with a late EPSP, which had a maximum amplitude in the stimulus frequency range of 2-5 Hz. 2. Very weak WM stimulation sometimes evoked EPSPs in isolation from IPSPs. The falling phase of the EPSP revealed voltage dependence characteristic to the responses mediated by N-methyl-D-aspartate (NMDA) receptors and was depressed by application of an NMDA antagonist DL-2-amino-5-phosphonovalerate (APV), whereas the rising phase of the EPSP was insensitive to APV. 3. The early EPSPs followed by IPSPs were insensitive to APV but were replaced with a slow depolarizing potential by application of a non-NMDA antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX), indicating that the early EPSP is mediated by non-NMDA receptors. The slow depolarization was mediated by NMDA receptors because it was depressed by membrane hyperpolarization or addition of APV. 4. The late EPSP evoked by higher-frequency stimulation was abolished by APV, indicating that it is mediated by NMDA receptors, which are located either on the recorded cell or on presynaptic cells to the recorded cells. 5. Long-term potentiation (LTP) of EPSPs was examined in cells perfused with solutions containing 1 microM bicuculline methiodide (BIM), a gamma-aminobutyric acid (GABA) antagonist. WM was stimulated at 2 Hz for 15 min as a conditioning stimulus to induce LTP, and the resultant changes were tested by low-frequency (0.1 Hz) stimulation of WM. 6. LTP of early EPSPs occurred in more than one-half of the cells (8/13) after strong conditioning stimulation. The rising slope of the EPSP was increased 1.6 times on average. 7. To test involvement of NMDA receptors in the induction of LTP in the early EPSP, the effect of conditioning stimulation was studied in a solution containing 100 microM APV, which was sufficient to block completely synaptic transmission mediated by NMDA receptors. LTP occurred in the same frequency and magnitude as in control solution.     

Dynamic modulation of excitation and inhibition during stimulation at gamma and beta frequencies in the CA1 hippocampal region

Fast oscillations at gamma and beta frequency are relevant to cognition. During this activity, excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) are generated rhythmically and synchronously and are thought to play an essential role in pacing the oscillations. The dynamic changes occurring to excitatory and inhibitory synaptic events during repetitive activation of synapses are therefore relevant to fast oscillations. To cast light on this issue in the CA1 region of the hippocampal slice, we used a train of stimuli, to the pyramidal layer, comprising 1 s at 40 Hz followed by 2--3 s at 10 Hz, to mimic the frequency pattern observed during fast oscillations. Whole cell current-clamp recordings from CA1 pyramidal neurons revealed that individual stimuli at 40 Hz produced EPSPs riding on a slow biphasic hyperpolarizing-depolarizing waveform. EPSP amplitude initially increased; it then decreased concomitantly with the slow depolarization and with a large reduction in membrane resistance. During the subsequent 10-Hz train: the cells repolarized, EPSP amplitude and duration increased to above control, and no IPSPs were detected. In the presence of GABA(A) receptor antagonists, the slow depolarization was blocked, and EPSPs of constant amplitude were generated by 10-Hz stimuli. Altering pyramidal cell membrane potential affected the time course of the slow depolarization, with the peak being reached earlier at more negative potentials. Glial recordings revealed that the trains were associated with extracellular potassium accumulation, but the time course of this event was slower than the neuronal depolarization. Numerical simulations showed that intracellular chloride accumulation (due to massive GABAergic activation) can account for these observations. We conclude that synchronous activation of inhibitory synapses at gamma frequency causes a rapid chloride accumulation in pyramidal neurons, decreasing the efficacy of inhibitory potentials. The resulting transient disinhibition of the local network leads to a short-lasting facilitation of polysynaptic EPSPs. These results set constraints on the role that synchronous, rhythmic IPSPs may play in pacing oscillations at gamma frequency in the CA1 hippocampal region.     

The effects of high Mg2+-to-Ca2+ ratios on frequency potentiation in hippocampal slices of young and aged rats

In some central systems, excitatory postsynaptic potential (EPSP) amplitude increases substantially during repetitive synaptic stimulation ("frequency potentiation"), as does the probability of spike generation. An apparently analogous phenomenon at the neuromuscular junction ("frequency facilitation") depends on residual Ca2+ in nerve terminals. However, the mechanisms of central frequency potentiation are not completely defined and it is therefore not clear whether the patterns of Ca2+-dependent synaptic plasticity are fully analogous in central and peripheral systems. In addition, an age-related deficit in hippocampal frequency potentiation has been previously described, and the degree of sensitivity of this deficit to Mg2+-to-Ca2+ balance could yield important insights into its nature. In these studies, we used the hippocampal slice preparation to examine the effects of varying Mg2+-to-Ca2+ ratios in the artificial cerebrospinal fluid (ACF) on frequency potentiation in aged and young rats. Extracellular and intracellular methods were used to assess the responses of hippocampal CA1 neurons during orthodromic stimulation of the monosynaptic Schaffer-commissural pathway. In experiment 1, frequency potentiation of the hippocampal population spike during 7-Hz stimulation was found to be significantly greater in an ACF with a high Mg2+-to-Ca2+ ratio (2.7) than in an ACF with a normal Mg2+-to-Ca2+ ratio (0.5), for both young and aged rat slices. Aged slices exhibited less frequency potentiation than young in both media. In experiment 2, the field EPSP and population spike were monitored concurrently, and the differences in Mg2+-to-Ca2+ ratio between the high Mg2+-to-Ca2+ ACF ratio (2.0) and normal Mg2+-to-Ca2+ ACF ratio (1.0) were reduced, to determine whether aged and young brains differed in sensitivity to smaller variations in Mg2+-to-Ca2+ balance. Under these conditions, the effects of high Mg2+-to-Ca2+ ratios on frequency potentiation (at 7 Hz) were found to be most pronounced in aged rat slices, particularly for potentiation of the spike. No effects were seen of age or Mg2+-to-Ca2+ ratios on presynaptic fiber volley amplitudes. Field EPSP (but not spike) amplitudes were reduced with aging, in an input-output (I/O) stimulation series at control frequency (0.2 Hz). However, the high Mg2+-to-Ca2+ ACF ratio of (2.0), which improved field EPSP frequency potentiation, did not decrease control field EPSP amplitudes in the I/O series. Therefore, the effects of high MG2+-to-Ca2+ ACF ratio on brain frequency potentiation seem to be mediated in part by mechanisms other than the classical reduction of release probability.(ABSTRACT TRUNCATED AT 400 WORDS)     

Adenosine inhibits the synaptic potentials in rat septal nucleus neurons mediated through pre- and postsynaptic A1-adenosine receptors

Intracellular and voltage-clamp recordings were made from neurons in rat brain slices containing dorsolateral septal nucleus (DLSN), in vitro. Bath application of adenosine (100 μM) produced a hyperpolarization (2–15 mV) in 46% of DLSN neurons (AH-neurons); in the remaining 54% neurons (non-AH-neurons), no hyperpolarization to adenosine was observed. Adenosine (1–300 μM) depressed not only the excitatory postsynaptic potential (EPSP) but also the inhibitory postsynaptic potential (IPSP) and the late hyperpolarizing potential (LHP) evoked by stimulation of the hippocampal CA3 area or the fimbria/fornix pathway in both AH- and non-AH-neurons. In non-AH-neurons, adenosine did not block current responses resulting from glutamate, muscimol or baclofen applied directly to DLSN neurons. In AH-neurons, adenosine partially depressed the baclofen-induced outward current. Adenosine did not block the directly-evoked IPSP (monosynaptic IPSP) as well as the glutamate-induced (hyperpolarizing) postsynaptic potential (PSP) that is mediated by GABA released from interneurons. These results suggest that adenosine does not directly inhibit the release of GABA. The effects of adenosine was mimicked by selective A₁-receptor agonists and was blocked by selective A₁-receptor antagonists. Pertussis toxin (PTX) blocked the hyperpolarization induced by adenosine or baclofen applied exogenously. Adenosine consistently produced presynaptic inhibition of the EPSP even in DLSN neurons treated with PTX. We conclude that adenosine inhibits neurotransmission between the hippocampus and septum through activation of pre- and postsynaptic A₁-receptors which couple with G-proteins of different PTX-sensitivity or with distinct transduction processes at pre- vs. postsynaptic sites.     

Excitatory and inhibitory postsynaptic potentials in alpha-motoneurons produced during fictive locomotion by stimulation of the mesencephalic locomotor region

We tested the hypothesis that stimulation of the mesencephalic locomotor region (MLR) activates polysynaptic pathways that project to lumbar spinal motoneurons and are involved in the initiation of locomotion. Fictive locomotion was produced by MLR stimulation, and intracellular records of evoked postsynaptic potentials (PSPs) in alpha-motoneurons were computer analyzed. Stimulation of sites in the MLR that were maximally effective for the initiation of locomotion produced excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in all the motoneurons examined. The amplitudes of the PSPs increased as locomotion commenced. The EPSPs were largest during the depolarized phase of the step cycle, and in 17 of our 22 cells the EPSP was replaced by an IPSP of slightly longer latency during the hyperpolarized phase. The mean latency of the EPSPs measured from the stimulus artifact produced by stimulation of the MLR was 5.1 ms (3.0-7.0 ms). In all cases, the IPSP occurred 0.6 ms or more after the onset of the EPSP in the same cell. Later PSPs were sometimes observed as well. The effects of constant current injection on the membrane potential oscillations associated with fictive locomotion (locomotor drive potentials) were examined. The results showed that the amplitudes of the locomotor drive potentials (LDPs) could be affected by depolarizing and hyperpolarizing current injection. The data is consistent with the LDP having a predominant inhibitory component, which is more readily altered by current injection than is the excitatory component. The effect of constant current injections on the MLR-evoked PSPs was also examined, and it was observed that both EPSPs and IPSPs could be affected by the injected currents. The EPSPs increased in amplitude with constant hyperpolarizing current injection, and this fact rules out the possibility that the EPSP is actually a reversed IPSP. The IPSP was decreased in amplitude by hyperpolarizing current injection. Combined stimulation of the MLR and the ipsilateral high-threshold muscle or cutaneous afferents produced facilitation of both short- and long-latency MLR-evoked PSPs, suggesting that the two pathways share common interneurons. The possibility that the long-latency PSPs are produced by rapid oscillation in the locomotor central pattern generator is discussed. We concluded that MLR stimulation that evokes fictive locomotion produces both excitation and inhibition of spinal motoneurons. Spinal interneuronal systems are implicated and may be those involved in the initiation and control of locomotion. The probable relay sites for the descending pathway from the MLR to motoneurons are discussed.     

Postsynaptic potentials recorded in neurons of the cat's lateral geniculate nucleus following electrical stimulation of the optic chiasm

1. We recorded intracellularly from X and Y cells of the cat's lateral geniculate nucleus and measured the postsynaptic potentials (PSPs) evoked from electrical stimulation of the optic chiasm. We used an in vivo preparation and computer averaged the PSPs to enhance their signal-to-noise ratio. 2. The vast majority (46 of 50) of our sample of X and Y cells responded to stimulation of the optic chiasm with an excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP); these were tentatively identified as relay cells. We quantified several parameters of these PSPs, including amplitude, latency, time to peak (i.e., rise time), and duration. 3. Among the relay cells, the latencies of both the EPSP and action potential evoked by optic chiasm stimulation were shorter in Y cells than in X cells. Furthermore, the difference between the latencies of the EPSP and action potential was shorter for Y cells than for X cells. This means that the EPSPs generated in Y cells reached threshold for generation of action potentials faster than did those in X cells. The EPSPs of Y cells also displayed larger amplitudes and faster rise times than did those in X cells, but neither of these distinctions was sufficient to explain the shorter latency difference between the EPSP and action potential for Y cells. 4. The EPSPs recorded in relay Y cells had longer durations than did those in relay X cells. Our data suggest that the subsequent IPSP actively terminates the EPSP, which, in turn, suggests that the time interval between EPSP and IPSP onsets is longer in Y cells than in X cells. Furthermore, we found that, for individual Y cells, the latency and duration of the evoked EPSP were inversely related. These observations lead to the conclusion that the latency of IPSPs activated from the optic chiasm is relatively constant among Y cells and thus independent of the EPSP latencies. Thus the excitation and inhibition produced in individual geniculate Y cells may originate from different populations of retinogeniculate axons. 5. The IPSPs recorded in geniculate relay cells following optic chiasm stimulation could be divided into three groups based on their durations. The majority of both X and Y cells showed short-duration IPSPs, whereas the remainder of Y cells displayed medium-duration IPSPs, and the remaining X cells displayed long-duration IPSPs. A positive correlation was seen between the time to peak and duration of these IPSPs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Posttetanic and frequency potentiation in slices of rat olfactory cortex

The electrical tetanization of the lateral olfactory tract at a frequency of 30/sec for 15 sec elicited the development of posttetanic potentiation of populational EPSP and IPSP in surviving slices of rat olfactory cortex. The stimulation of the lateral olfactory tract by series of stimuli at a constant frequency of 10/sec and with intervals of 4–5 sec between series facilitates the emergence of the phenomenon of frequency potentiation. The data obtained indicate that such forms of functional plasticity as posttetanic and frequency potentiation are manifested in the pyriform cortex.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 76, No. 4, pp. 425–429, April, 1990.     

Distribution of potentiation following short high frequency bursts to motoneurons of different rheobase

Summary Potentiation of composite EPSPs has been studied at group Ia fiber/alpha motoneuron connections using a short burst of conditioning stimuli [32 shocks with 6 ms interstimulus interval (ISI)]. Potentiation reached its peak (range 1.2–2.0 X control value) 100–150 ms following the burst. Potentiation decayed slowly and was still present 2 s after the burst. High frequency burst stimulation of a nerve to a synergist muscle did not potentiate the response to stimulation of the homonymous nerve. Three independent sets of measurements suggest that the time course of decline of potentiation depends on the amount of transmission during the potentiated state. First, connections on high rheobase motoneurons exhibited more peak potentiation than those on low rheobase motoneurons but potentiation decayed more rapidly in the former than in the latter. Second, increasing the frequency of the conditioning burst enhanced peak potentiation but the rate of decay of this potentiation also increased. Third, potentiated EPSPs exhibited more low frequency depression than unpotentiated ones at the same connection suggesting that low frequency stimulation during the potentiated state could elevate the rate of decay of potentiation. The short burst paradigm could cause peak potentiation similar in magnitude to that evoked by long, high frequency trains (studied here at the same connection) but with much less of an increase in latency and rise time of the potentiated EPSP. The magnitude of potentiation was unrelated to changes in EPSP latency and rise time. These findings indicate that potentiation can act to modulate EPSP amplitude under conditions of normal motor behaviour when spindle afferents fire in patterns similar in duration and frequency to those used in the present experiments.     

Effects of ventral hippocampal long-term potentiation and depression on the gamma-band local field potential in anesthetized rats

We examined the effect of long-term potentiation or depression (LTP or LTD) on the local field potential, focusing on the gamma-band (40–100 Hz) power, in the ventral hippocampus CA1 of anesthetized rats. LTP and LTD induction in the CA3–CA1 pathway increased the CA1 spontaneous gamma-band power by around 40 and 80–100 Hz, respectively, while neither changed the evoked levels significantly. These results suggest that the ventral CA1 local field potential can maintain bidirectional plasticity in the steady state for the long term. Given the involvement of synaptic plasticity in learning and memory, the gamma-band power change associated with LTP/LTD may relate to ventral hippocampal functions. The LTP increased the spontaneous power at around 40 Hz of the gamma-band frequency in the ventral CA1, and the LTD did the same at 80–100 Hz. The biphasic increase may distribute the subsequent input appropriately to regulate the relevant synaptic history in the ventral CA1 and anatomically related structures in vivo.     

Inhibitory role of dentate hilus neurons in guinea pig hippocampal slice

1. Current and voltage-clamp recording of CA3/CA4 pyramidal neurons, hilar neurons, and granule cells or pairs of these neurons were used to study the generation of Cl-dependent and K-dependent inhibitory postsynaptic potentials (IPSPs) in the guinea pig hippocampal slice preparation. 2. A sequence of an early Cl-dependent and a late K-dependent IPSP was evoked in CA3 neurons by electrical stimulation from the stratum moleculare of the dentate gyrus, the hilus, and the stratum oriens/alveus. Blockade of glutamatergic excitation by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and D(-)-2-amino-5-phosphonovaleric acid (APV, 30 microM) abolished IPSPs evoked from the stratum moleculare of the dentate gyrus, but IPSPs could still be evoked from the hilus and the stratum oriens/alveus. 3. Repetitive giant IPSPs, which consisted of Cl-dependent and K-dependent components, were evoked by bath application of 4-aminopyridine (4-AP, 10-50 microM) in CA3 neurons and in granule cells. Giant IPSPs were blocked by bath-applied tetrodotoxin (TTX). In addition, 4-AP hyperpolarized CA3 neurons in a Cl-dependent and picrotoxin-sensitive way. 4. Focal application of TTX to the dentate gyrus or the hilus considerably reduced the amplitude of giant IPSPs evoked by 4-AP in CA3 neurons. In hilar neurons, 4-AP evoked repetitive bursts, eventually, but not necessarily intermingled with giant IPSPs. Bursts were observed in hilar neurons in presence as well as absence of CNQX and APV. 5. In paired recordings, bursts in hilar neurons induced by 4-AP occurred simultaneously to giant IPSPs in granule cells and CA3 neurons, and giant IPSPs in granule cells occurred simultaneously to giant IPSPs in CA3 neurons. Blockade of glutamatergic excitation by CNQX and APV did not abolish this synchrony. 6. 4-AP-evoked Cl- and K-dependent IPSPs were, unlike electrically evoked IPSPs, not strictly coupled: some 20% of large IPSPs and up to 90% of small IPSPs were either Cl or K dependent. In granule cells K-dependent components either preceded or followed Cl-dependent components. 7. K-dependent IPSPs only could be evoked in CA3 neurons by focal application of 4-AP (1 mM) to the hilus, the stratum lacunosum moleculare or the stratum pyramidale. Wash out of Ca for 15-20 min blocked the Cl-dependent but not the K-dependent component of giant IPSPs evoked by bath-applied 4-AP.(ABSTRACT TRUNCATED AT 400 WORDS)     

Ephaptic interactions contribute to paired pulse and frequency potentiation of hippocampal field potentials

Summary The contribution of ephaptic interactions to potentiation of the hippocampal CA1 extracellular population spike during paired pulse or frequency stimulation of stratum radiatum (SR) inputs was investigated using the in vitro hippocampal slice preparation. Records of the transmembrane potential revealed a depolarizing wave with an amplitude and latency that varied directly with that of the extracellular population spike. Paired pulse or repetitive stimulation of SR resulted in a potentiation of the population spike amplitude and a corresponding increase in the amplitude of the TMP depolarizing wave. Action potentials generated during the stimulus train consistently arose from the peak of the depolarizing wave. It is proposed that ephaptic interactions contribute to potentiation of the extracellular population spike through recruitment of subthreshold neurons within the population during repetitive afferent stimulation.Supported by the Medical Research Council of Canada to JJM. RWT supported by a MRC Studentship and TLR by a BCHCRF Training Fellowship     

Hyperbaric pressure depresses potentiation of polysynaptic medullospinal reflexes in newborn rats

Hyperbaric pressure induces hyperexcitability and convulsions in intact animals by mechanisms that are not understood. In the present experiments we examined the effects of pressure on medullospinal reflexes and synaptic interactions in in vitro brainstem-spinal cord of newborn rats. Reflex activity was recorded extracellularly from the cut ventral root of the 1st cervical nerve; the Vth and Xth cranial nerves were stimulated. Exposure to pressure of 10.1 MPa increased the amplitude and duration of individual reflex responses. Hyperbaric pressure inhibited post-tetanic potentiation, reduced recovery time and decreased the marked heterosynaptic potentiation caused by Vth nerve stimulation on the Xth nerve reflex. Xth nerve stimulation caused weak heterosynaptic potentiation of the Vth nerve reflex and was not affected by pressure. In contrast to crustacean neuromuscular junction, hyperbaric pressure in the mammalian central nervous system enhanced single polysynaptic responses but depressed frequency-dependent potentiation of medullospinal reflexes.