Current-distance relations of axons mediating circling elicited by midbrain stimulation

Stimulation of mediocaudal midbrain in rats produces ipsiversive circling due to the stimulation of longitudinal axons. The refractory periods of these axons were measured by delivering trains of conditioning and testing pulses via a single electrode at various conditioning-testing (C-T) intervals. As C-T interval increased from 0.3 to 2.0 ms, the frequency required to produce a constant amount of circling halved. The current-distance relations of these axons were measured by placing two electrodes lateral to one another, and delivering conditioning pulses via one electrode and testing pulses via the second electrode. The required frequency decreased less at C-T intervals in the refractory period range using two electrodes rather than using a single electrode. This partial refractoriness suggests that only part of the axons were stimulated by both electrodes. The refractoriness increased as current increased or as interelectrode distance decreased. The overlap in the fields of stimulation at each current was calculated from the refractoriness observed in single and double electrode experiments. The results suggest that the axons mediating circling have a wide range of thresholds rather than a single threshold. The current required to activate an axon is roughly equal to K X r2, were K is a constant and r is the radial distance from electrode to axon. K must range from 400 to at least 3000 microA/mm2, to account for the circling data. For axons mediating medial forebrain bundle self-stimulation3, K must range from 1000 to at least 6400 microA/mm2. Estimation of the K distribution allows calculation of the effects of electrode size, placement and current on the recruitment of axons with different thresholds.     

Increase in diameter of the axonal initial segment is an early change in amyotrophic lateral sclerosis

We measured the diameter of the most distal portion of the axonal initial segment, the neuronal size of anterior horn cells, and the length of the axon hillock plus the initial segment (AH+IS) in the lumbar spinal cord in motor neuron disease. Three patients with amyotrophic lateral sclerosis (ALS) and one with lower motor neuron disease (LMND) were compared with 11 controls. Serial plastic sections stained with toluidine blue and electron micrographs were studied. A total of 214 axons directly emanating from the somata (n = 207) and the primary dendrites (n = 7) were observed in the patients. Approximately 19% of the proximal myelinated axons (24 axons out of 155 in ALS, and 17 axons out of 59 in LMND) were swollen at the first internode, and most of the swellings extended to the middle portion of the initial segment. Electron microscopy showed that the swellings of the proximal axons (the initial segment and the first internode) directly connected with their somata consisted mainly of accumulations of 10-nm neurofilaments. The average diameter of the most distal initial segment was markedly larger in ALS (n = 155) (P < 0.0001) and LMND (n = 59) (P < 0.0001) than in the controls (n = 258). Moreover, the average diameter of the most distal portion of even normal-appearing initial segments of the non-swollen axons was larger in ALS (n = 131) (P < 0.0001) than in the controls. The perikarya and axon hillocks connected with the normal-appearing and swollen proximal axons and their dendrites almost always appeared normal. These findings suggest that increase in diameter of the axonal initial segment which reflects the abnormal accumulation of neurofilaments represents an early pathological change in motor neuron disease and that the slow axonal transport of neurofilaments is probably impaired in this portion of the axon at an early stage in the disease process. The average size of the normal-appearing cell bodies from which axons emanated was smaller in ALS (P < 0.0001) and LMND (P < 0.0001) than in the controls. There was no significant difference in the AH+IS length among ALS having normal-appearing initial segment, LMND, and controls.     

Posterior hypothalamic stimulation of anesthetized normothermic and hypothermic rats evokes shivering thermogenesis

Normothermic (37°C), anesthetized Long Evans rats given unilateral electrical stimulation (0.5 ms monophasic pulses of 100–300 μA at 50 Hz for 30 s) of the posterior hypothalamus (PH) had graded, sustained increases in EMG electrical activity of the gastronemius muscle (i.e. shivering). In a current-related manner, gastronemius muscle temperatures (T_m immediately increased following PH stimulation, surface temperature (T_t did not change and colonic (core, T_c temperatures initially fell, then subsequently rose after the applied stimulus. A biphasic pressor response occurred after PH electrical stimulation associated with tachycardia. PH electrical stimulation (0.5 ms pulses at 50 Hz for 30 s ofonly 40 μA) induced shivering in anaesthetized, hypothermic Long Evans rats undergoing acute cold exposure. When these same hypothermic rats were cooled further to cause shivering, PH electrical stimulation (0.5 ms pulses at 50 Hz for 30 s ofonly 40 μA) induced further increases in the shivering response (↑ EMG area of gastronemius muscle) from the shivering response before PH stimulation. Results indicate that electrical stimulation of the PH can evoke shivering in anesthetized normothermic rats. Stimulation of the PH with lower current intensity can induce or increase shivering of hypothermic rats previously exposed to the cold.     

Amphetamine-induced changes in nigrostriatal terminal excitability are modified following repeated amphetamine pretreatment

To investigate neural mechanisms associated with behavioral sensitization to amphetamine, we studied the effect of an intrastriatal infusion of amphetamine on nigrostriatal axon terminal electrical excitability in rats following withdrawal from repeated systemic treatment. Rats were injected with amphetamine 2.5 mg/kg s.c. or saline daily for 4 days. Either 24 h or 14 days after the last injection, extracellular recordings were obtained from dopaminergic neurons of the substantia nigra, in a blind design in which the experimenter did not know the pretreatment regime. In order to assess the electrical excitability of the nigrostriatal axonal field, neurons were activated antidromically by stimulating their terminal fields in the striatum. As previously reported, striatal infusion of amphetamine (1 μM/0.3 μl) in control animals resulted in a significant reduction in excitability as indicated by an increase in striatal stimulus current necessary to evoke antidromic activity. In contrast, intrastriatal amphetamine administration to amphetamine-pretreated animals did not decrease excitability. Spontaneous firing rates and patterns of cell discharge did not differ between saline and amphetamine-treated animals. The chronic amphetamine-induced change in the effect of an acute intrastriatal amphetamine infusion on nigrostriatal terminal excitability may be due to enduring alterations in the amphetamine-induced release of dopamine and other striatal neurotransmitters or to changes in the sensitivity of presynaptic hetero and/or autoreceptors on the dopaminergic axons.     

Nitric oxide induces an increased Na conductance in identified neurons of Aplysia

The ionic mechanism of the effects of micropressure ejections of hydroxylamine (HOA) and sodium nitroprusside (SNP), nitric oxide (NO) generators, on the membrane of identified neurons (R9–R12) of Aplysia kurodai was investigated with conventional voltage-clamp, micropressure ejection, and ion-substitution techniques. Micropressure ejection of HOA and SNP onto the neurons caused a marked depolarization in the unclamped neurons. Clamping the same neurons at their resting potential level (−60 mV) and reejecting HOA and SNP with the same dose produced a slow inward current (I_i(HOA) and I_i(SNP), 3–7 nA in amplitude, 15–60 s in duration) associated with an increase in input membrane conductance. Bath-applied hemoglobin (50 μM), a nitric oxide scavenger, almost completely blocked I_i(HOA) and I_i(SNP), and 3-isobutyl-1-methylxanthine (IBMX, 50 μM) prolonged and enhanced both I_i(HOA) and I_i(SNP). An intracellular injection of cyclic guanosine 3′,5′-monophosphate (cGMP) into the same neurons produced a slow inward current (I_i(cGMP)) which resembled the responses to HOA and SNP, and this current was enhanced in IBMX. Bath-applied methylene blue (10 μM), an inhibitor of guanylate cyclase, significantly reduced I_i(HOA) and I_i(SNP). The inward currents induced by HOA, SNP and cGMP were sensitive to changes in the external Na⁺ concentration. These results suggest that extracellular NO can induce a slow inward current associated with an increase in Na⁺ conductance, mediated by an increase in intracellular cGMP.     

Temporal evolution and spatial distribution of the diffusion constant of water in rat brain after transient middle cerebral artery occlusion

The regional distribution and temporal evolution of the diffusion coefficient (D_w) of water in rat brain was measured during and after transient middle cerebral artery (MCA) occlusion. Male Wistar rats (n = 14) were subjected to 2 h of middle cerebral artery occlusion, induced by intracarotid insertion of a filament. Diffusion (n = 14) and perfusion (n = 7) weighted magnetic resonance imaging were performed before, and at various time points after MCA occlusion, ranging from 30 min up to 7 days. Our data demonstrate that the temporal profiles of D_w differ between the severely and the least damaged regions of tissue. In the core of the lesion, where the tissue evolved to necrosis, D_w declined significantly (P < 0.001) within 0.5 h after onset of ischemia, and remained depressed until 24 h after withdrawal of the suture. However, no statistically significant decline in D_w was found in the perifocal regions containing morphologically intact cells. Perfusion MRI qualitatively exhibited a hypoperfusion and reperfusion during, and after 2 h MCA occlusion, respectively. A significant (r ≥ 0.71, P < 0.01) correlation was found between ΔD_w (the difference in D_w between the ipsilateral ischemic and homologous contralateral control regions) obtained immediately before withdrawal of the suture (2 h of ischemia) and at specific early time points after withdrawal of the suture, and the degree of ischemic cell damage. No significant (P > 0.01) correlation was detected at an early time points of ischemia or at other time points after withdrawal of the suture. Our data suggest that values for ΔD_w obtained at 2 h, during the period of MCA occlusion and at specific early time points after withdrawal of the suture, are highly correlated to the histological outcome of the tissue, and both ΔD_w and the temporal profile of D_w may reflect underlying biophysical changes in the tissue evoked by the ischemic insult.     

Electrical characteristics of neurons in the motor region of the cat cerebral cortex]

Electrical parameters of motor cortex neurons were studied in acute experiments on cats. Input resistance of cortical neurons varied from few to some tens of Momega (mean value 11.11 +/- 3.93 Momega). A hyperbolic relation between threshold current and input resistance for cortical neurons was found. Velocity of axon conduction and input resistance are negatively correlated. Time constant of the membrane (to) was 7.1 +/- 3.46 ms. In some neutrons a second time constant t1= 1.65 +/- 0.36 ms was also found. Using result of Rall's model, the electronic length of the dendrite was computed, it was found to be 3.66-0.94 in units of length constant. These data are compared with those obtained on motoneurons. Functional significance of electrical parameters of cortical neurons is discussed.     

Single motor axon conduction velocities of human upper and lower limb motor units. A study with transcranial electrical stimulation.

OBJECTIVES: To calculate conduction velocities (CV) of single motor axons innervating hand, forearm and leg muscles, weak anodal electrical transcranial stimuli were used and single motor unit potentials were recorded in 17 normal subjects. METHODS: The central motor conduction time and neuromuscular transmission delay were subtracted from the latency of unit response to cortical stimulation and single motor axon CV were calculated. RESULTS: In extensor indicis proprius (EIP) units, CV ranged from 30.3 to 76.1m/s (mean: 51.3 +/- 7.1m/s, 139 units). In first dorsal interosseous (FDI), they ranged from 45.1 to 66.2m/s (mean: 54.6 +/- 2.6m/s, 88 units). In tibialis anterior (TA), velocities ranged from 27.8 to 55.9m/s (mean: 41.3 +/- 7.5m/s, 123 units). In FDI units, velocities were compared with those obtained with the F-wave method (range: 50.3-64.5m/s, mean: 58.1 +/- 2.0m/s). CONCLUSIONS: Compared with previously published values, the present method gives better access to slow-conducting units, first recruited by transcranial stimulation and voluntary effort. The spectrum of individual CV was much broader for EIP and TA than for FDI. A linear decline of maximal CV with age was observed, while minimal CV were not affected, suggesting that aging causes a selective loss of the fastest-conducting units.     

Double-pulse stimulation of startle-like responses in rats: refractory periods and temporal summation

A startle-like response was evoked by electrical stimulation with one pulse in several brainstem sites of the primary acoustic startle circuit. If a second pulse was delivered 0.4-10 ms after the first pulse, a stronger response or a decreased current threshold resulted. The facilitatory effect of the second pulse increased as interpulse (C-T) interval increased from 0.4 to 2.0 ms in cochlear nucleus or ventral lateral lemniscus sites. In caudal pontine reticular formation sites, the effect of the second pulse increased sharply from 0.3 to 0.5 ms. These results suggest that very short refractory period axons mediate electrically elicited startle in reticular formation, and that longer refractory period axons mediate startle in cochlear nucleus or ventral lateral lemniscus. In reticular formation sites, the effect of the second pulse declined nearly exponentially from 2.0 to 50 ms with a time constant of about 4 ms. Stimulation of similar reticular formation sites in cats evokes monosynaptic EPSPs in spinal motoneurons with an almost identical time course, as reported by other investigators. This suggests that the startle response evoked from the reticular formation results from monosynaptic activation of spinal motoneurons. Temporal summation declined more slowly and irregularly in cochlear nucleus and ventral lateral lemniscus sites, suggesting that these sites are not monosynaptically connected with spinal motoneurons, a conclusion consistent with anatomical data. In reticular formation sites near the facial nerve, a second peak in the two-pulse curve was observed at a C-T interval of 10 ms. The second peak was blocked by local anesthesia of the face ipsilateral to the stimulating electrode, suggesting that a single twitch of facial muscles facilitates startle.     

Electrophysiological characterization of sodium channel types in the HCN-1A human cortical cell line

Electrically evoked sodium currents were recorded under whole-cell patch clamp from undifferentiated HCN-1A cells. Peak sodium currents had a half-maximal activation, V_m0.5, of −22.6 ± 1.0 mV with a voltage dependence, K_m, of 7.28 ± 0.39 mV⁻¹. Steady-state inactivation indicated the presence of two types of sodium channel. One type inactivated with V_h0.5 = −93.8 ± 1.2 mV and k_h = −6.8 ± 0.4 mV⁻¹. The second type of sodium channel inactivated w V_h0.5 = −44.6 ± 1.5 mV and k_h = −7.3 ± 0.4 mV⁻¹. The occurrence of each channel type varied from cell to cell and ranged from 0 to 100% of the total sodium current. No variation in the rate of inactivation was seen when the holding potential was adjusted to eliminate the more negative of the two inactivation components. Application of tetrodotoxin (TTX) or saxitoxin (STX) revealed channel types with two different affinities for each toxin. TTX blocked peak sodium conductance with apparent IC50s of 22 nM and 5.3 μM. STX was more potent, with apparent IC₅₀s of 1.6 nM and 1.2 μM. There was no statistical correlation between toxin sensitivity and steady-state inactivation voltage, suggesting that these properties varied independently among sodium channel types.     

Properties of antidromically activated callosal neurons and neurons responsive to callosal input in rabbit binocular cortex

Extracellular spikes were recorded from the cell bodies of antidromically activated callosal axons in the binocular visual cortex of unanesthetized, unparalyzed rabbits. Callosal axons were stimulated near their terminals in the contralateral cortex. Recordings were also obtained from neurons which responded synaptically to contralateral cortical stimulation. The primary method for differentiating antidromic from synaptic activation was the test for collision of impulses. Additional tests provided further confirmation of antidromic activation. Units which sent an axon across the corpus callosum (callosal neurons) were thereby distinguished from units which responded synaptically to callosal input. Eighteen percent of units sampled sent an axon across the corpus callosum. The median conduction velocity of callosal axons was less than 2 m/sec. An additional 18% of units encountered were synaptically activated by contralateral cortical stimulation. Callosal neurons were found to differ from synaptically activated units in three distinct ways. Callosal neurons had very low spontaneous firing rates (median =< 1.0 spike/sec), responded with a single spike to contralateral cortical stimulation and never responded to diffuse flash illumination. In contrast, most synaptically activated units demonstrated high spontaneous firing rates (median = 10.2 spikes/sec), responded with a burst of spikes to contralateral cortical stimulation and were also driven by diffuse flash illumination.     

Discharges of neurons of the frog tectum during electric stimulation of individual retinal ganglion cells

In the frog optic tectum, at the depth of 200-270 micron extracellular monosynaptic PSPS of one axon were recorded under threshold electrical stimulation of the retina by a short train of stimuli. The latency of presynaptic spike was 8-12 ms. At a 5-25 ms interval between successive stimuli a negative spike was observed on the top of the testing EEG quanta enlarged 1.5-2.5 times. This spike is considered to be a population discharge evoked by the firing of a single fibre of the optic tract. This fibre terminates in layer F or G, while the population spike is generated by the tectum units of layers 6-8. A possibility that the firing of the 3d-5th class detectors excites tectal ganglionic cells whose axons form the main part of the tectobulbospinal tract is discussed.     

Antidromic activation of spikes with bimodal and trimodal latencies in the olfactory bulb of rabbits

Spikes with bimodal and occasional trimodal latencies were recorded from neurons in the olfactory bulb of rabbits in response to lateral olfactory tract (LOT) stimulation at one site. Among neurons with bimodal spike latencies, two types have to be distinguished. In the case of type I neurons long-latency second-mode spikes were suppressed by short-latency first-mode spikes. Due to this suppression the long-latency second-mode spike could be investigated only, when its threshold was lower than that of the short-latency spike. In the case of type II neurons the long-latency second-mode spike was not suppressed. The collision test was applied to type I bimodal spikes. All short-latency first-mode and long-latency second-mode spikes were suppressed by spontaneous spikes. The suppression time indicated the likelihood of collision in most cases, but one could not entirely exclude the possibility, that short-latency first-mode spikes were suppressed due to refractoriness and long-latency second-mode spikes due to inhibition. To allow a more definite interpretation of collision a multiple collision test was applied, by stimulating axons at several LOT sites. A parallel rise of latency values and suppression time values was measured for 3 and more axonal spikes with different latencies, indicating collision and antidromic activation more definitely. Antidromically activated short-latency first-mode spikes were interpreted to be due to axonal stimulation and antidromically activated long-latency second-mode spikes to be due to axon collateral stimulation. No evidence for any postsynaptic activation of type I short-latency first-mode or long-latency second-mode spikes was gained. An indicator for collision of an antidromic spike with a spontaneous spike is the value collision time minus latency (c-l). The c-l values of axonal spikes ranged from 0.2 to 1.8 ms with a mean of 0.7 ms (n = 25), and c-l values of axon collateral spikes from 0.2 to 2.5 ms, with a mean of 1.1 ms (n = 13). The interpretation of c-l values is discussed. In the multiple collision test the c-l deviations from the lowest c-l value of each neuron ranged for axonal spikes between 0.0 and 0.7 ms (n = 25), with 38% not exceeding 0.1 ms and 81% not exceeding 0.4 ms. Spikes activated via axon collaterals had c-l deviations between 0.0 and 2.0 ms (n = 13). The c-l deviations above 2 ms were remote from other values and considered to be possibly inhibitory.(ABSTRACT TRUNCATED AT 400 WORDS)     

The refractory period of fast conducting corticospinal tract axons in man and its implications for intraoperative monitoring of motor evoked potentials.

OBJECTIVE: To determine the absolute and relative refractory period (RRP) of fast conducting axons of the corticospinal tract in response to paired high intensity (HI or supramaximal) and moderate intensity (MI or submaximal) electrical stimuli. The importance of the refractory period of fast conducting corticospinal tract axons has to be considered if repetitive transcranial electrical stimulation (TES) is to be effective for eliciting motor evoked potentials (MEPs) intraoperatively. METHODS: Direct (D) waves were recorded from the epidural space of the spinal cord in 14 patients, undergoing surgical correction of spinal deformities. To assess the absolute and RRPs of the corticospinal tract, paired transcranial electrical stimuli at interstimulus intervals (ISI) from 0.7 to 4.1 ms were applied. Recovery of conditioned D wave at short (2 ms) and long (4 ms) ISI was correlated with muscle MEP threshold. The refractory period for peripheral nerve was tested in comparison to that for the corticospinal tract. In four healthy subjects sensory nerve action potentials of the median nerve were studied after stimulation with paired stimuli. RESULTS: HI TES revealed a mean duration of 0.82 ms for the absolute refractory period of the corticospinal tract, while MI stimulation resulted in a mean refractory period duration of 1.47 ms. Stimuli of HI produced faster recovery of D wave amplitude during the RRP. Furthermore, short trains of transcranial electrical stimuli did not elicit MEPs when D wave showed incomplete recovery. A similar influence of stimulus intensity on recovery time was found for the refractory period of peripheral nerve. CONCLUSIONS: The recovery of D wave amplitude is dependent upon stimulus intensity. High intensity produces fast recovery. This is an important factor for the generation of MEPs. When HI TES is used to elicit MEPs, short and long ISIs are equally effective. When MI TES is used to elicit MEPs, only a long ISI of 4 ms is effective.     

Currents evoked by GABA and glycine in acutely dissociated neurons from the rat medial preoptic nucleus

The responses of acutely dissociated medial preoptic neurons to application of GABA and glycine were studied using the perforated-patch whole-cell recording technique under voltage-clamp conditions. GABA, at a concentration of 1 mM, evoked outward currents in all cells (n=33) when studied at potentials positive to −80 mV. The I–V relation was roughly linear. The currents evoked by GABA were partially blocked by 25–75 μM picrotoxin and were also partially or completely blocked by 100–200 μM bicuculline. Glycine, at a concentration of 1 mM, did also evoke outward currents in all cells (n=12) when studied at potentials positive to −75 mV. The I–V relation was roughly linear. The currents evoked by glycine were largely blocked by 1 μM strychnine. In conclusion, the present work demonstrates that neurons from the medial preoptic nucleus of rat directly respond to the inhibitory transmitters GABA and glycine with currents that can be attributed to GABA_A receptors and glycine receptors respectively.     

Two substrates for medial forebrain bundle self-stimulation: myelinated axons and dopamine axons

The directly activated substrates for medial forebrain bundle (MFB) self-stimulation are primarily low threshold, myelinated axons with absolute refractory periods of 0.4 to 1.2 msec, conduction velocities of 1 to 8 m/sec and current-distance constants of 1000 to 3000 microA/mm2. When small electrode tips or high currents are used, however, a second population of long refractory period (1.2 to 5 msec) axons is added. The excitability properties of this second population are almost identical with those of dopamine (DA) axons. Furthermore, the long-refractory period effects of MFB self-stimulation are reduced, but not completely blocked, by peripheral injections of alpha-flupenthixol, suggesting that dopamine axons make small contributions to MFB self-stimulation when small tips are used. Collision data, strength-duration data and refractory period data in various self-stimulation experiments are compared. Asymmetric collision effects, recently observed in cortical and striatal sites mediating electrically evoked turning, may help determine where synapses are located in circuits mediating electrically evoked behaviors. A neural model of symmetric, asymmetric and mixed collision is proposed.     

Ultrastructural immunocytochemical localization of the dopamine D2 receptor and tyrosine hydroxylase in the rat ventral pallidum.

The mesopallidal dopamine system plays a role in locomotor activity and reward. To understand the potential contribution of the dopamine D2 receptor (D2R) to the action of dopamine in the ventral pallidum (VP), we used electron microscopic immunocytochemistry to examine the cellular and subcellular localization of an antipeptide antiserum against the D2R in both ventromedial and dorsolateral VP compartments. In each region the majority of the total D2R-labeled profiles (n = 1,132) were axon terminals (55%) and small unmyelinated axons (27%). These terminals were often apposed to other axon terminals or dendrites and formed almost exclusively symmetric, inhibitory-type axodendritic synapses. Immunogold D2R labeling in axon terminals was seen on the plasmalemma and membranes of nearby synaptic vesicles. In ventral pallidal sections processed for dual detection of D2R peptide and the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH), D2R labeling was detected in a few axons and axon terminals containing TH immunoreactivity as well as in axons contacted by TH-labeled terminals. In most cases, however, the D2R-labeled profiles were located at a distance from small axons and terminals containing TH. Our results provide the first ultrastructural evidence that D2Rs in the two VP subterritories are strategically located for primary involvement in modulation of the presynaptic release of nondopaminergic inhibitory transmitters. They also suggest that in this region the presynaptic D2 receptors are 1) minimally involved in autoregulation of dopaminergic transmission, and 2) differentially activated by dopamine, depending in part on levels and distance from release sites.     

Luzindole,a melatonin receptor antagonist,inhibits the transient outward K+ current in rat cerebellar granule cells

The inhibitory effect of the melatonin receptor antagonist luzindole on voltage-activated transient outward K⁺ current (I_K(A)) was investigated in cultured rat cerebellar granule cells using the whole cell voltage-clamp technique. At the concentration of 1 μM to 1 mM, luzindole reversibly inhibited I_K(A) in a concentration-dependent manner. In addition to reducing the current amplitude of I_K(A),luzindole accelerated the fast inactivation of I_K(A) channels and shifted the curves of voltage-dependent steady-state activation and inactivation of I_K(A) by +6.6 mV and −7.0 mV, respectively. The inhibitory effect of luzindole was neither use-dependent nor voltage-dependent, suggesting that the binding affinity of luzindole to I_K(A) channels is state-dependent. Including luzindole in the pipette solution, or extracellular application of 4 P-PDOT, an antagonist of melatonin receptors, did not change the luzindole-induced inhibitory effect on the I_K(A) current, indicating that luzindole exerts its channel blocking inhibitory action at the extracellular mouth of the channel, and that the effect is not due to action of the melatonin receptors. Our data are the first demonstration that luzindole is able to block transient outward K⁺ channels in rat cerebellar granule cells in a state-dependent manner, likely associated with extracellular interaction of the drug with the I_K(A) inactivation gate.     

Effects of lesions of various brain areas on drug priming or footshock-induced reactivation of extinguished conditioned place preference

The effect of Radix paeoniae rubra (RPR) on voltage-gated sodium channel (VGSC) currents (I_Na) was examined in freshly isolated rat hippocampal CA1 neurons using whole-cell patch-clamp technique under voltage-clamp conditions. RPR suppressed I_Na without affecting the current activation, inactivation and deactivation. The amplitude of I_Na decreased by 18.4% within a few seconds of 0.8 mg/ml RPR exposure. RPR (0.8 mg/ml) shifted the steady-state inactivation curves of I_Na to negative potentials, with hyperpolarizing direction shift of V_1/2 of 10.0 mV. The time course of I_Na recovery from inactivation was prolonged significantly by 0.8 mg/ml RPR. RPR (0.8 mg/ml) also enhanced the activity-dependent attenuation of I_Na and decreased the fraction of activated channels. These results suggested that RPR suppressed hippocampal CA1 I_Na by shifting the inactivation curve in hyperpolarizing direction, slowing the recovery time course from inactivation, enhancing the activity-dependent attenuation and decreasing the number of activatable channels. RPR suppression on I_Na might predict the protective effect during brain ischemia in hippocampal CA1 neurons.     

Contraversive circling elicited from the internal capsule and substantia nigra: evidence for a continuous axon bundle mediating circling

Electrical stimulation of many brain sites (e.g., anteromedial cortex, internal capsule, substantia nigra, superior colliculus, rostro-medial tegmentum, and medial pons) evokes circling. The collision method of Shizgal et al. (J. Comp. Physiol. Psychol., 94 (1980) 227-237) was used to determine whether these sites are functionally connected for the production of circling in rats. If connectivity was evidenced, then refractory period and conduction velocity distributions were determined for axons passing through the connected stimulation sites. Collision of up to 90% was found between electrodes placed in internal capsule and substantia nigra, suggesting that these sites are connected by continuous axons that mediate circling. The refractory periods of these axons ranged from 0.5 to 4.5 ms, and the conduction velocities of these axons ranged from 0.9 to 4.4 ms. These velocities are similar to those of striatonigral axons. No collision was found between anteromedial cortex and any other sites tested, nor between pontine sites and internal capsule or substantia nigra.