Hindlimb unweighting for 2 weeks alters physiological properties of rat hindlimb motoneurones

We sought to determine whether decreased neuromuscular use in the form of hindlimb unweighting (HU) would affect the properties of innervating motoneurones. Hindlimb weight-bearing was removed in rats for a period of 2 weeks via hindlimb suspension by the tail. Following this the electrophysiological properties of tibial motoneurones were recorded under anaesthesia in situ . After HU, motoneurones had significantly ( P < 0.05) elevated rheobase currents, lower antidromic spike amplitudes, lower afterhyperpolarization (AHP) amplitudes, faster membrane time constants, lower cell capacitances, and depolarized spike thresholds. Frequency–current ( f – I ) relationships were shifted significantly to the right (i.e. more current required to obtain a given firing frequency), although there was no change in f – I slopes. 'Slow' motoneurones (AHP half-decay times, > 20 ms) were unchanged in proportions in HU compared to weight-bearing rats. Slow motoneurones had significantly lower minimum firing frequencies and minimum currents necessary for rhythmic firing than 'fast' motoneurones in weight-bearing rats; these differences were lost in HU rats, where slow motoneurones resembled fast motoneurones in these properties. In a five-compartment motoneurone model with ion conductances incorporated to resemble firing behaviour in vivo , most of the changes in passive and rhythmic firing properties could be reproduced by reducing sodium conductance by 25% and 15% in the initial segment and soma, respectively, or by increasing potassium conductance by 55% and 42%, respectively. This supports previous conclusions that changes in chronic neuromuscular activity, either an increase or decrease, may result in physiological adaptations in motoneurones due to chronic changes in ion conductances.     

Repetitive firing in layer V neurons from cat neocortex in vitro

Input-output relations of large neurons from layer V of cat sensorimotor cortex were studied in an in vitro slice preparation using steps and ramps of intracellularly injected current. Depolarization attained during the interspike interval (ISI) was compared to the voltage levels required to activate a previously described (29) persistent sodium current (INaP). INaP was studied using a single-electrode voltage clamp in the same cells tested for firing behavior. Following an injected current step, firing rate declined smoothly to a steady level with a time course that was approximately exponential in most cells (tau, 9-43 ms). In most cells, the relation between firing rate and injected current (f-I relation) consisted of two linear segments, both for adapted, steady firing and for early intervals during adaptation. The slope of the steeper, initial (or sole) linear segment of the f-I curve averaged 26.2 Hz/nA during steady firing and was steeper when plotted for early interspike intervals. The variation of the depolarization at which spike initiation occurred (firing level) and the membrane potential between rhythmic spikes was examined during adaptation and steady firing. In most cells, firing level rose rapidly during a rhythmic train to a steady value. The steady firing level attained remained unchanged over a wide range of steady firing rates. Nevertheless, the mean depolarization during the interspike interval (V) increased approximately linearly with steady firing rate. Even at the slowest firing rates, V is sufficient to activate INaP. The use of injected current ramps demonstrated that neocortical cells were sensitive to rate of change of stimulus current (dI/dt) as well as its amplitude (I). The use of ramps followed by steady currents demonstrated that the repetitive response lagged behind changes in stimulus parameters and did not reach a steady state even during slow ramps; i.e., the response depended on time as well as on I and dI/dt. Instantaneous firing rate during the ramp increased linearly with time for a wide range of ramp slopes (dI/dt). The instantaneous firing rate of early interspike intervals was also linearly related to ramp slope for small ramp slopes. In spite of these linear relationships, quantitative analysis indicated that firing rate during ramp stimulation cannot, in general, be described by a simple linear combination of separate amplitude- and rate-dependent terms. The repetitive firing properties of the in vitro neurons are compared to those of in vivo neocortical neurons and other cell types.(ABSTRACT TRUNCATED AT 400 WORDS)     

Essential role of a fast persistent inward current in action potential initiation and control of rhythmic firing

In spinal motoneurons in an in vivo preparation, we investigated the relationship between a fast persistent inward current located in or near the soma and the capacity of these cells to fire rhythmically. The fast persistent current could be markedly reduced by prolonged depolarization. Modest reductions resulted in profound changes in the slope of the frequency-current relationship. At greater reduction levels, rhythmic firing failed and could not be restored by increasing injected current. However, fully formed spikes still occurred in a slow, uncoordinated fashion, suggesting that the fast inactivating Na(+) currents that generate the spike itself remained unchanged. Consequently, the fast persistent inward current, which may be primarily generated by persistent Na(+) channels, appears to be essential for initiation of spikes during rhythmic firing. Additionally, it appears that the fast persistent current plays a major role in setting the frequency-current gain.     

Intracellular study of electrophysiological features of primate spinothalamic tract neurons and their responses to afferent inputs

1. Intracellular recordings were made from 43 spinothalamic (STT) neurons in the lumbosacral region of the spinal cord in anesthetized macaque monkeys. The antidromic responses of these neurons to electrical stimulation of the ventral posterior lateral (VPL) nucleus of the thalamus were examined, and orthodromic responses to electrical stimulation of the sural nerve or to mechanical stimulation of hindlimb skin were recorded to study the electrophysiological features of these neurons and their responses to afferent inputs. 2. The resting membrane potential of the neurons ranged from -26 to -70 mV and the antidromic latency from 2.3 to 9.1 ms. Three of the neurons were located in lamina 1 and were recorded so briefly that only antidromic and spontaneous activity could be studied. The rest of the neurons were located in laminae III-V and were of the wide-dynamic-range (WDR) type. 3. The antidromic action potentials recorded in the somas of STT neurons typically showed a fast rising phase and a short initial segment-somadendritic (IS-SD) delay. After repetitive antidromic stimulation, a progressive elongation of the IS-SD delay, widening of the spike, and failure of the SD spike were observed. 4. The afterpotential of the antidromic action potential consisted of a fast afterhyperpolarization (AHPf) and sometimes a delayed depolarization (DD) and a slow afterhyperpolarization (AHPs). The amplitude and the duration of the AHPs were progressively increased when longer trains of stimuli were used. When the membrane potential was hyperpolarized, the amplitude of the AHPs decreased, suggesting an involvement of K+ and/or Cl- ions. However, the AHPs completely disappeared when the strength of stimulation was adjusted to a level just below the threshold for the axon, suggesting that it was unlikely that recurrent inhibition contributed to the AHPs. 5. The background activity of 32 STT neurons was analyzed. The membrane potential at which spikes were triggered in these neurons was around -42 mV. The width and the rise time of the spontaneous spikes were shorter than those of antidromic action potentials, although the maximum rate of rise was similar. The heights of the spontaneous spikes were slightly shorter than those of antidromic action potentials. 6. Three types of background activity have been observed. One type had a very low average spontaneous rate with a bursting firing pattern, consisting of a few spikes superimposed on a depolarization. This type of activity was seen mostly in lamina I neurons. The second type of activity had a moderate to high spontaneous rate with a fairly constant interval between spikes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Relationship between repetitive firing and afterhyperpolarizations in human neocortical neurons.

1. Human neocortical neurons fire repetitively in response to long depolarizing current injections. The slope of the relationship between average firing frequency and injected current (f-I slope) was linear or bilinear in these cells. The mean steady-state f-I slope (average of the last 500 ms of a 1-s firing episode) was 57.8 Hz/nA. The instantaneous firing rate decreased with time during a 1-s constant-current injection (spike frequency adaptation). Also, human neurons exhibited habituation in response to a 1-s current stimulus repeated every 2 s. 2. Afterhyperpolarizations (AHPs) reflect the active ionic conductances after action potentials. We studied AHPs with the use of intracellular recordings and pharmacological manipulations in the in vitro slice preparation to 1) gain insight into the ionic mechanisms underlying the AHPs and 2) elucidate the role that the underlying currents play in the functional behavior of human cortical neurons. 3. We have classified three AHPs in human neocortical neurons on the basis of their time courses: fast, medium, and slow. The amplitude of the AHPs was dependent on stimulus intensity and duration, number and frequency of spikes, and membrane potential. 4. The fast AHP had a reversal potential of -65 mV and was eliminated in extracellular Co2+, tetraethylammonium (TEA) or 4-aminopyridine, and intracellular TEA or CsCl. These manipulations also caused an increase in spike width. 5. The medium AHP had a reversal potential of -90 to -93 mV (22-24 mV hyperpolarized from mean resting potential). This AHP was reduced by Co2+, apamin, tubocurare, muscarine, norepinephrine (NE), and serotonin (5-HT). Pharmacological manipulations suggest that the medium AHP is produced in part by 1) a Ca-dependent K+ current and 2) a time-dependent anomalous rectifier (IH). 6. The slow AHP reversed at -83 to -87 mV (14-18 mV hyperpolarized from mean resting potential). This AHP was diminished by Co2+, muscarine, NE, and 5-HT. The pharmacology of the slow AHP suggests that a Ca-dependent K+ current with slow kinetics contributes to this AHP. 7. The currents involved in the fast AHP are important in spike repolarization, control of interspike interval during repetitive firing, and prevention of burst firing. Currents underlying the medium and slow AHPs influence the interspike interval during repetitive firing and produce spike frequency adaptation and habituation.     

Slow oscillatory firing: a major firing pattern of dopamine neurons in the ventral tegmental area

Using spectral analysis and in vivo single-unit recording in rats, the present study revealed a pronounced slow oscillation (SO) in the firing activity of about half the dopamine (DA) neurons recorded in the ventral tegmental area. DA neurons in this group tended to fire repetitive spike clusters, making them appear to be rhythmic bursting cells. However, only some of these burst-like events met the traditional "80/160 ms" burst criteria entirely. The observation that the SO could be found in nonbursting DA cells, occurred at frequencies different from those of bursts, and persisted after bursts were digitally removed from spike trains further supports the suggestion that the SO is different from the traditionally defined bursting. Interspike intervals (ISIs) had been thought to be bimodally distributed in bursting DA neurons. This study found that some nonbursting DA cells also had a bimodal ISI distribution and a significant number of bursting cells did not. In the majority of cells where less than half the spikes occurred in bursts, a bimodal ISI distribution was highly predictive of the presence of the SO. Results further showed that the generation of the SO required forebrain inputs to DA neurons but not the adrenergic alpha1 receptor activation responsible for psychostimulant-induced increases in the SO. Taken together, these results suggest that the SO is distinct from the traditionally defined bursting and represents a major firing pattern of DA neurons in the ventral tegmental area.     

Arrhythmic firing in dopamine neurons of rat substantia nigra evoked by activation of subthalamic neurons.

Intracellular recordings were made from dopaminergic neurons of the rat substantia nigra compacta (SNc) in in vitro slice preparations to study the synaptic influence from the subthalamic nucleus (STh). After microstimulation of STh, monosynaptic excitatory postsynaptic potentials (EPSPs) were produced in dopaminergic neurons. STh-induced EPSPs were composed of 6-cyano-7-nitroquinoxalene-2,3-dione- and 2-amino-5-phosphonovaleric acid-sensitive components. Subthreshold EPSPs evoked by STh stimulation could differentially trigger pacemaker-like slow depolarization (PLSD) and low-threshold Ca2+ spike (LTS) depending on the level of baseline membrane potentials. When a subthreshold EPSP was evoked by STh stimulation during rhythmic firing, the STh-induced EPSP could shift or elevate PLSD to a more depolarized level, resulting in generation of a spike at an earlier arrhythmic timing to restart the rhythmic firing. The interspike interval after the arrhythmic spike remained almost unchanged. In contrast, when a suprathreshold EPSP for evoking spikes was produced by STh stimulation during rhythmic firing, the STh-induced spike was just interposed between two spontaneous spikes the interspike interval of which was almost the same as those seen during the preceding rhythmic firing. This ectopically induced spike did not disturb or reset rhythmic firing. It was concluded that SNc dopaminergic neurons receive monosynaptic glutamatergic inputs from STh, and subthreshold and suprathreshold EPSPs evoked by STh stimulations can induce two types of arrhythmic firing in SNc dopaminergic neurons, similar to arrhythmic occurrences of the QRS complex seen in the electrocardiogram of the atrial and ventricular arrhythmias, respectively. The former arrhythmic firing may play a crucial role in desynchronization of dopaminergic neurons.     

Repetitive firing of CA1 hippocampal pyramidal cells elicited by dendritic glutamate: slow prepotentials and burst-pause pattern

Summary (1) In order to compare responses to dendritic vs. somatic depolarization, CA1 pyramidal cells in rat hippocampal slices were stimulated by iontophoresis of glutamate to sensitive spots in the dendrites, and by somatic current injection. (2) Low intensities of either stimulus elicited slow repetitive firing. Each action potential was preceded by a slow depolarizing prepotential (SPP), lasting 50–300 ms and was followed by fast (3–5 ms) and slow (more than 100 ms) afterhyperpolarizations (AHPs). The SPPs, and AHPs were indistinguishable for the two types of stimuli. (3) In response to strong depolarizations, most cells showed an initial burst of spikes, followed by a pause before the steady discharge. This pattern was elicited by both glutamate and current. (4) The input resistance usually increased 5–20% during subthreshold depolarizations by glutamate or current. In contrast, large doses of glutamate caused a slow decline in the resistance (up to 40%), which was larger than during comparable current-induced discharge, and the response was followed by a longer AHP. (5) It is concluded that both dendritic and somatic depolarization, induced by glutamate and current, respectively, can elicit sustained repetitive firing with SPPs, fast and slow AHPs and burst-pause pattern, thus, increasing the likelihood that these phenomena play a role during natural activation of CA1 cells.     

A comparison of extracellular and intracellular recordings from medial septum/diagonal band neurons in vitro.

Firing patterns, action potential characteristics and some active membrane properties of guinea-pig medial septum/diagonal band neurons were studied in an in vitro slice preparation. A comparison was made between several types of cells classified according to either extracellularly recorded (n = 130) or intracellularly recorded (n = 30) electrophysiological characteristics. Using multi-barrel extracellular electrodes, three principal cell types were distinguished: slow rhythmic firing cells (29%), fast rhythmic firing cells (65%) and burst-firing cells (6%). Most slow firing cells could also be distinguished from other cell types by their relatively longer action potential duration and a characteristic cadmium-sensitive "hump" in the repolarization phase of the action potential. These characteristics of slow firing cells matched well with the characteristics of cholinergic, slow afterhyperpolarization cells previously identified with intracellular recordings. The action potential shape, firing rate and firing pattern characteristics of about 60% of extracellularly recorded fast rhythmic firing cells matched those of previously identified non-cholinergic fast afterhyperpolarization cells. The remaining extracellularly recorded, rhythmic firing cells (about 10% of slow firing and 40% of fast firing cells) had a mixture of characteristics which precluded unequivocal classification as to cholinergic or non-cholinergic cell type. Using intracellular recording, the bee venom toxin, apamin, was shown to attenuate the characteristic post spike slow afterhyperpolarization of cholinergic cells and greatly enhanced their firing rate to depolarizing pulses. Apamin often attenuated a smaller and more transient afterhyperpolarization found in identified non-cholinergic cells, but firing rate was increased only slightly. Extracellular recordings from slow and fast rhythmic firing cells in the presence of apamin showed that excitability of slow firing cells was enhanced significantly more than fast firing cells. The apamin data support the hypothesis that extracellularly recorded slow firing cells are cholinergic. We conclude that extracellularly recorded medial septum/diagonal band cells characterized by broad action potentials, slow rhythmic firing under microiontophoresed glutamate and a signature "hump" in the falling phase of the action potential are cholinergic cells. Extracellularly recorded fast rhythmic firing cells with a narrow action potential and no "hump" in the action potential are likely to be non-cholinergic cells. This extracellular electrophysiological "fingerprint" for cholinergic medial septum/diagonal band cells in vitro may now be extended to studies in vivo where controversy remains as to the neurochemical identity of basal forebrain cells involved in control of hippocampal slow rhythmic activity.     

Ephaptically generated potentials in CA1 neurons of rat's hippocampus in situ

Passive (ephaptic) transmembrane currents generated by antidromically evoked electrical fields were studied in CA1 hippocampal neurons of urethan-anesthetized rats. Recording was mostly from the stratum pyramidale where the fields have a maximum (negative) amplitude. The antidromic population spike was consistently smaller when recorded inside a noninvaded neuron rather than extracellularly. This indicated a substantial transmembrane potential (Vm), which was revealed and quantified by subtracting from the intracellular record a just-extracellular one. In neurons that have spikes greater than or equal to 40 mV (mean 60 mV), the average Vm was 41.1% of the extracellular field (Ve; mean 6.7 mV). Typically, Vm was very brief (mean duration 1.1 ms), predominantly monophasic, and in a depolarizing direction. Though almost synchronous with Ve, the peak of Vm was most often delayed slightly. Its amplitude varied with the intensity of antidromic stimulation, bearing an approximately constant relation to Ve, and it was not markedly sensitive to large changes in membrane potential. Most of these features confirm its ephaptic nature. By contrast, no consistent Vm was recorded from unresponsive cells, presumed to be glia. When combined with subthreshold depolarizing pulses, antidromic fields increased the firing probability of cells not activated by the antidromic stimulus. The ephaptic nature of this excitation was indicated by its very short latency, too early to be of synaptic origin, a much greater jitter of spike latency than was seen with antidromic spikes, and its inability to follow repetitive stimulation at frequencies as low as 2 Hz. In addition, juxta-threshold ephaptic excitations showed the random patterns of firing and very steep relation to intensity of stimulation expected of single-unit responses to electrical stimulation. In general, much larger excitatory effects could be demonstrated in neurons that had a high threshold for antidromic activation. The correlation between Vm and the increase in firing probability (r = 0.85) was strongly positive. A significant excitatory effect was detectable with antidromic fields as small as 1 mV. These ephaptically generated transmembrane potentials are probably of functional significance, even under physiological conditions, particularly in promoting synchronized firing of CA1 neurons. In the APPENDIX, the predictions of a simple neuronal model as a lumped resistance and capacitance circuit are shown to agree quite well with the observations.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of antidromic discharges in crayfish primary afferents

Contrary to orthodromic spikes that are generated in sensory organs and conveyed to CNS, antidromic spikes are generated in the axon terminals of the sensory neurons within the CNS and are conveyed to the peripheral sensory organ. Antidromic discharges are observed in primary afferent neurons of both vertebrates and invertebrates and seem to be related to the rhythmic activity of central neural networks. In this study, we analyzed the effect of antidromic discharges on the sensory activity of a leg proprioceptor in in vitro preparations of the crayfish CNS. Intracellular microelectrodes were used both to record the orthodromic spikes and to elicit antidromic spikes by injecting squares pulses of depolarizing current at various frequencies. Experiments were performed on the three types of identified sensory afferents (tonic, phasotonic, and phasic). The main results showed a reduction of the firing frequency of the orthodromic activity in 82% of the tested afferents. In tonic afferents, during their occurrences and according to their frequency, antidromic spikes or bursts reduced or suppressed the orthodromic activity. Following their terminations, they also induced a silent period and a gradual recovery of the orthodromic activity, both of which increased as the duration and the frequency of the antidromic bursts increased. In phasotonic and phasic afferents, antidromic bursts reduced or suppressed the phasic responses as their frequency and durations increased. In phasotonic afferents, if elicited prior to the movements, long-duration bursts with increasing frequency reduced more rapidly the tonic background activity than the phasic one whereas short-duration bursts at high frequency produced strong decreases of both. The effect of antidromic bursts accumulated when they are repetitively elicited. Antidromic bursts induced a much larger decrease of the sensory activity than adaptation alone. The occurrences of antidromic spikes or bursts may have a functional role in modulating the incoming sensory messages during locomotion. The mechanisms by which antidromic spikes modulate the firing sensitivity of the primary afferents may well lie in modifications of the properties of either mecanotransduction and/or spike initiation.     

Responses of mitral/tufted cells to orthodromic and antidromic electrical stimulation in the olfactory bulb of the tiger salamander

1. Responses evoked by electrical stimulation of the olfactory nerve and olfactory tracts were analyzed in 46 output cells of the salamander olfactory bulb, in vivo. Labeling of several cells with horseradish peroxidase indicated that they were mitral and/or tufted neurons. The responses contained reproducible sequences of depolarizing and hyperpolarizing potentials, which changed with increases in stimulus intensity. 2. Stimulation of the nerve with intensities subthreshold for evoking spikes in the recorded cell resulted in a small depolarization followed by a period of hyperpolarization, during which spontaneous spikes were suppressed. With suprathreshold stimulus intensities, a single spike or often a burst of spikes was evoked, followed by a complex prolonged hyperpolarization. When full spikes were blocked by injecting hyperpolarizing current through the recording electrode, an excitatory postsynaptic potential (EPSP) with two major components and sometimes a fast prepotential were observed at the beginning of the response. Amplitudes of the EPSP and hyperpolarization increased with graded increases in stimulus intensity. In tests with paired stimulus volleys, spike generation was inhibited for at least 1 s and often for several seconds during the hyperpolarization. 3. Stimulation of the tracts with intensities subthreshold for evoking spikes in the recorded cell resulted in a complex prolonged hyperpolarization. With suprathreshold stimulus intensities, a single spike was evoked, followed by a similar period of hyperpolarization. When full spikes were blocked by injecting hyperpolarizing current through the recording electrode, a small antidromic spike, presumably generated in the axon or initial segment, was often observed. Amplitude of the hyperpolarization increased with graded increases in stimulus intensity. In tests with paired volleys, generation of a full antidromic spike was inhibited for a period that usually began 20-30 ms, following the spike evoked by the conditioning stimulus and lasted 100-500 ms. Full antidromic spikes were evoked prior to the period of inhibition and small antidromic spikes were evoked during the period. 4. The mean latencies of single evoked spikes or the first spikes of bursts decreased from 22 to 17 ms with increases in the intensity of nerve stimulation and from 7 to 6 ms with increases in the intensity of tract stimulation. Only decreases in orthodromic latency were significant at P less than or equal to 0.05, as determined by one-sided t tests between the means of responses subdivided according to response pattern and relative stimulus intensity.(ABSTRACT TRUNCATED AT 400 WORDS)     

Ionic currents and firing patterns of mammalian vagal motoneurons in vitro

The electrophysiological properties of guinea-pig dorsal vagal motoneurons were studied in an in vitro slice preparation. Antidromic, orthodromic and direct stimulation of the neurons demonstrated that the action potential is comprised of several distinct components: a fast initial spike followed by afterdepolarization and an early and a late afterhyperpolarizations. The fast initial spike and the early afterhyperpolarization were blocked by tetrodotoxin and tetraethylammonium ions, respectively. The afterdepolarization (present on the falling phase of the spike) and the late afterhyperpolarization were blocked by the addition of ions known to block calcium conductance (CdCl2, CoCl2 or MnCl2), indicating close association between these two potentials. Prolonged outward current injection through the recording electrode produced two different firing patterns, depending on the initial level of the membrane potential. From resting potential (usually -60 mV) the firing pattern was characterized by a short train of action potentials appearing shortly after the onset of the depolarization step. By contrast, when the depolarization was delivered from a hyperpolarized membrane potential level, a short train of repetitive firing appeared after an initial delay of 300-400 ms. The membrane current responsible for this initial reduction in excitability was studied by means of a single-electrode voltage-clamp technique. The magnitude, direction and kinetics of such current flow are consistent with the presence of early potassium current (IA), partly inactive at the resting potential. Synaptic activation of vagal motoneurons could be obtained by electrical stimulation of the tissue surrounding the vagal nucleus or by direct activation of the vagal nerve. Perivagal stimulation generated excitatory and inhibitory synaptic potentials which could be reversed by shifting the membrane potential. Vagal nerve stimulation, in addition to the antidromic activation of the cells, generated depolarizing responses which were unitary in nature and did not show much sensitivity to shifts in membrane potential. Perivagal and vagal nerve-evoked depolarizations could generate action potentials as well as partial dendritic spikes. We conclude that spike electroresponsiveness in vagal motoneurons is generated by voltage-dependent Na+ and Ca2+ conductances. In addition, the Ca2+-dependent current triggers a K+ conductance which is responsible for modulating the firing frequency obtained from the normal resting level.(ABSTRACT TRUNCATED AT 400 WORDS)     

Nonlinear systems analysis of the hippocampal perforant path-dentate projection. II. Effects of random impulse train stimulation

1. Nonlinear systems analytic techniques were used to characterize transformational properties of the network of neurons activated by perforant path input to the rabbit hippocampus. Trains of 4,064 impulses with randomly varying interimpulse intervals were used to stimulate perforant path fibers, and amplitudes of evoked dentate granule cell population spikes were measured. Interimpulse intervals of the random stimulus train were determined by a Poisson distribution with a mean interimpulse interval of 500 ms, and with intervals ranging from 1 to 5,000 ms. The response of dentate granule cells to this stimulation was assumed to reflect activity in the larger hippocampal network, because other subpopulations of neurons activated monosynaptically and polysynaptically within the hippocampal formation contribute to granule cell excitability through multiple feedforward and feedback pathways. System properties were characterized both for halothane anesthetized and chronically implanted, unanesthetized preparations. 2. Second-order kernel analysis showed that population spike amplitude was highly dependent on interimpulse interval. When population spikes of all latencies were included in the same analysis, stimulation impulses produced near-total suppression of spike amplitude when they were preceded 10-20 ms by another impulse in the train. Spike suppression extended to approximately 50 ms and was inversely related to length of the interimpulse interval. Suppression of granule cell response to intervals within the range of 10-50 ms was not influenced by halothane anesthesia. 3. Interstimulus intervals greater than approximately 50 ms resulted in a facilitation of population spike amplitude, with maximum facilitation occurring in response to intervals of 90-100 ms. The magnitude of maximum facilitation was significantly greater for anesthetized (129%) than for unanesthetized (74%) preparations. The range of intervals resulting in facilitation for unanesthetized animals could extend to 1,000-1,100 ms (average range, 61-714 ms). This was much greater than observed for population spikes recorded from anesthetized animals (50-364 ms), which exhibited suppression in response to intervals of approximately 300-700 ms. 4. Further analysis revealed that the nature of nonlinearities in population spike amplitude may depend on spike latency. For example, population spikes of "short" latency (3-4 or 4-5 ms, depending on the animal) exhibited only facilitation in response to interstimulus intervals of 1-4 ms.(ABSTRACT TRUNCATED AT 400 WORDS)     

Responses of rat substantia nigra pars reticulata units to cortical stimulation.

In order to study the function of multiple pathways between the sensorimotor cortex (Cx) and the substantia nigra pars reticulata (SNr), responses of SNr units to stimulation of the Cx were studied in anesthetized rats. Most of the units (229 of 236) exhibited repetitive firing with fairly short, regular intervals. The other 7 units displayed long duration spikes, irregular firing intervals and slow spontaneous firing. Stimulation of the Cx usually resulted in a short latency excitation and occasionally a long latency inhibition in both types of units. When strong stimulation was applied, multiple excitatory and inhibitory responses alternating each other with about a 25 ms interval were observed. SNr units responded with different patterns and latencies to stimulation of different sites of the sensorimotor Cx. The results indicate that signals derived from the sensorimotor Cx reach the SNr via multiple pathways and converge on many SNr neurons.     

Current- and voltage-clamp recordings and computer simulations of Kenyon cells in the honeybee

The mushroom body of the insect brain is an important locus for olfactory information processing and associative learning. The present study investigated the biophysical properties of Kenyon cells, which form the mushroom body. Current- and voltage-clamp analyses were performed on cultured Kenyon cells from honeybees. Current-clamp analyses indicated that Kenyon cells did not spike spontaneously in vitro. However, spikes could be elicited by current injection in approximately 85% of the cells. Of the cells that produced spikes during a 1-s depolarizing current pulse, approximately 60% exhibited repetitive spiking, whereas the remaining approximately 40% fired a single spike. Cells that spiked repetitively showed little frequency adaptation. However, spikes consistently became broader and smaller during repetitive activity. Voltage-clamp analyses characterized a fast transient Na+ current (INa), a delayed rectifier K+ current (IK,V), and a fast transient K+ current (IK,A). Using the neurosimulator SNNAP, a Hodgkin-Huxley-type model was developed and used to investigate the roles of the different currents during spiking. The model led to the prediction of a slow transient outward current (IK,ST) that was subsequently identified by reevaluating the voltage-clamp data. Simulations indicated that the primary currents that underlie spiking are INa and IK,V, whereas IK,A and IK,ST primarily determined the responsiveness of the model to stimuli such as constant or oscillatory injections of current.     

Tonic rhythmic activity of rat cerebellar neurons

Simultaneous recordings of multiple single unit activity in both cerebral and cerebellar cortex, cortical EEG, and both nuchal and vibrissal EMG were obtained in nine unrestrained rats. Putative Purkinje cells of the deep vermal cerebellar cortex exhibited rhythmic discharge of simple spikes with extremely low variability in interspike intervals for several hours. The highly rhythmic nature of spike discharge was remarkably stable across all states of sleep (both slow-wave and rapid eye movement sleep) and wake including quiet waking, grooming, eating, running in a familiar environment, and exploring a novel environment. The frequencies at which oscillatory discharges took place varied, among different cells, between 16 and 142 Hz; however, 75% of the recorded cells discharged at frequencies between 20 and 50 Hz. From recordings in which two to four such cells were recorded simultaneously, evidence was found for multiple cells firing at the same frequency as well as for multiple cells firing at different frequencies. The precise timing of spike discharge in these cells makes them potential candidates to participate in timing functions thought to depend on the cerebellum     

Intracellular recordings from medial septal neurons during hippocampal theta rhythm

 The electrophysiological properties of neurons of the medial septal nucleus and the nucleus of the diagnonal band of Broca (MS/DB) were studied using intracellular methods in urethane-anesthetized rats. Three types of rhythmically bursting neurons were identified in vivo on the basis of their action potential shapes and durations, afterhyperpolarizations (AHPs), membrane characteristics, firing rates and sensitivities to the action of muscarinic antagonist: (1) Cells with short-duration action potentials and no AHPs (2 of 34 rhythmic cells, 6%) had high firing rates and extremely reliable bursts with 6–16 spikes per theta cycle, which were highly resistant to scopolamine action. (2) Cells with short-duration action potentials and short-duration AHPs (8 of 34 rhythmic cells, 24%) also had high firing rates and reliable bursts with 4–13 spikes per theta cycle, phase-locked to the negative peak of the dentate theta wave. Hyperpolarizing current injection revealed a brief membrane time constant, time-dependent membrane rectification and a burst of firing at the break. Depolarizing current steps produced high-frequency repetitive trains of action potentials without spike frequency adaptation. The action potential and membrane and characteristics of this cell type are consistent with those described for GABAergic septal neurons. Many of these neurons retained their theta-bursting pattern in the presence of muscarinic antagonist. (3) Cells with long-duration action potentials and long-duration AHPs (24 of 34 rhythmic cells, 70%) had low firing rates, and usually only 1–3 spikes per theta cycle, locked mainly to the positive peak of the dentate theta rhythm. Hyperpolarizing current injection revealed a long membrane time constant and a break potential; a depolarizing pulse caused a train of action potentials with pronounced spike frequency adaptation. The action potential and membrane properties of this cell type are consistent with those reported for cholinergic septal neurons. The theta-related rhythmicity of this cell type was abolished by muscarinic antagonists. The phasic inhibition of ”cholinergic” MS/DB neurons by ”GABAergic” MS/DB neurons, followed by a rebound of their firing, is proposed as a mechanism contributing to recruitment of the whole MS/DB neuronal population into the synchronized rhythmic bursting pattern of activity that underlies the occurrence of the hippocampal theta rhythm. Received: 5 February 1996 / Accepted: 6 November 1996     

Oscillations of the spontaneous slow-wave sleep rhythm in lateral geniculate nucleus relay neurons of behaving cats

Intracellular recordings of 31 lateral geniculate nucleus relay neurons were performed in darkness in behaving cats in order to analyse electrical postsynaptic events which appeared during slow-wave sleep. A specific pattern characterized slow-wave sleep: a rapid depolarizing potential arising from baseline initiated a slow depolarization lasting for 40-60 ms which in turn most often elicited delayed fast spikes. This pattern recurred at a frequency of 6-12/s. The slow depolarizations were voltage dependent, usually not separated by any obvious phasic hyperpolarization and showed refractoriness. Other rapid depolarizing potentials occurring during the time course or at the end of a slow depolarization could have generated spike(s) but were followed by a rapid decay. Slow depolarizations were not observed during arousal or paradoxical sleep when the neurons tonically depolarized and displayed either rapid depolarizing potentials with a fast decay or repetitive firing and long high frequency bursts. In five of the studied neurons, decreases in frequency of the spontaneous rapid depolarizing potentials occurred during slow-wave sleep for 3-30 s oscillatory periods without any change in the behavioural state. During these periods all of the few remaining rapid depolarizing potentials arose from a flat baseline, had a higher amplitude and initiated a slow depolarization which always elicited a spike or burst of spikes after a brief delay. The slow-wave sleep rhythm decreased to 1-5/s. Simultaneously the baseline membrane potential hyperpolarized by a few millivolts and reached a level for reversal of inhibitory postsynaptic potentials. Imposed hyperpolarization of the membrane during wakefulness did not reveal any slow depolarization. But strong synaptic excitatory inputs and direct excitation (a break of the current pulse) from a hyperpolarized membrane did evoke the slow depolarization and eventually the fast spike(s) in both control and oscillatory neurons. A rhythm similar to that of slow-wave sleep was elicited during wakefulness by optic tract stimulation and was enhanced by membrane hyperpolarization. But under these conditions the rhythm was initiated by a phasic hyperpolarization and was composed of an alternating hyperpolarization-depolarization. Spontaneously and synaptically evoked rapid depolarizing potentials arising from baseline had a similar rising slope. The spontaneous ones initiated a slow depolarization leading to fast spike(s) during slow-wave sleep and could directly generate fast spike(s) during wakefulness.(ABSTRACT TRUNCATED AT 400 WORDS)     

Abnormal spontaneous and harmaline-stimulated Purkinje cell activity in the awake genetically dystonic rat

The genetically dystonic rat is an autosomal recessive mutant with a movement disorder that closely resembles the generalized dystonias seen in humans. Abnormal activity of neurons within the cerebellar nuclei is critical to the dystonic rat motor syndrome. Increased glutamic acid decarboxylase activity, increased glucose utilization, and decreased muscimol binding within the cerebellar nuclei of the dystonic rat suggests that Purkinje cell firing rates are increased in these animals. However, under urethane anesthesia, Purkinje cell simple spike firing rates in dystonic rats were less than half the rates seen in normal littermates. In this study, both spontaneous and harmaline-stimulated single-unit Purkinje cell recordings were obtained from awake normal and dystonic rats. In striking contrast to previous results obtained under urethane anesthesia, there was no statistically significant difference in average Purkinje cell spontaneous simple spike frequency between dystonic and normal rats. Similar to previous studies obtained under urethane anesthesia, Purkinje cell spontaneous complex spike frequency was much lower in dystonic than in normal rats. Many Purkinje cells from dystonic rats, particularly those from the vermis or older animals, exhibited rhythmic bursting simple spike firing patterns. Cross-correlations showed that complex spikes produced less suppression of simple spikes in dystonic than in normal rats and harmaline-stimulated complex spike activity was, on average, faster and more rhythmic in normal than in dystonic rats. These findings indicate that olivocerebellar network abnormalities in the dystonic rat are not due to an inability of Purkinje cells to fire at normal rates and suggest that abnormal Purkinje cell bursting firing patterns in the dystonic rat are due to a defect in the pathway from the inferior olive to climbing fiber synapses on Purkinje cells.