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Function of specific K⁺ channels in sustained high-frequency firing of fast-spiking neocortical interneurons

JOURNAL OF NEUROPHYSIOLOGY 1999年第5期82卷 2476-2489页

作者： Erisir, A Lau, D Rudy, B Leonard, CS New York Med Coll Dept Physiol Valhalla NY 10595 USA NYU Sch Med Dept Biochem New York NY 10016 USA NYU Sch Med Dept Physiol & Neurosci New York NY 10016 USA

Function of specific K+ channels in sustained high-frequency firing of fast-spiking neocortical interneurons. J. Neurophysiol. 82: 2476-2489, 1999. Fast-spiking GABAergic interneurons of the neocortex and hippocampus fire high-frequency trains of brief action potentials with little spike-frequency adaptation. How these striking properties arise is unclear, although recent evidence suggests K+ channels containing Kv3.1-Kv3.2 proteins play an important role. We investigated the role of these channels in the firing properties of fast-spiking neocortical interneurons from mouse somatosensory cortex using a pharmacological and modeling approach. Low tetraethylammonium (TEA) concentrations (less than or equal to 1 mM), which block only a few known K+ channels including Kv3.1-Kv3.2, profoundly impaired action potential repolarization and high-frequency firing. Analysis of the spike trains evoked by steady depolarization revealed that, although TEA had little effect on the initial firing rate, it strongly reduced firing frequency later in the trains. These effects appeared to be specific to Kv3.1 and Kv3.2 channels, because blockade of dendrotoxin-sensitive Kv1 channels and BK Ca2+-activated K+ channels, which also have high TEA sensitivity, produced opposite or no effects. Voltage-clamp experiments confirmed the presence of a Kv3.1-Kv3.2-like current in fast-spiking neurons, but not in other interneurons. Analysis of spike shape changes during the spike trains suggested that Naf channel inactivation plays a significant role in the firing-rate slowdown produced by TEA, a conclusion that was supported by computer simulations. These findings indicate that the unique properties of Kv3.1-Kv3.2 channels enable sustained high-frequency firing by facilitating the recovery of Na+ channel inactivation and by minimizing the duration of the afterhyperpolarization in neocortical interneurons.

关键词：动作电位/药物作用动作电位/生理学诱发电位海马/生理学中间神经元/药物作用中间神经元/生理学小鼠近交C57BL 新皮质/生理学神经元/药物作用神经元/生理学神经肽类/药物作用神经肽类/生理学钾通道/药物作用钾通道/生理学钾通道电压门控反应时间回归分析 Shaw钾通道躯体感觉皮质/药物作用躯体感觉皮质/生理学四乙基铵/药理学动物小鼠

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Source of inappropriate receptive fields in cortical somatotopic maps from rats that sustained neonatal forelimb removal

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JOURNAL OF NEUROPHYSIOLOGY 1999年第2期81卷 625-633页

作者： Lane, RD Stojic, AS Killackey, HP Rhoades, RW Med Coll Ohio Dept Neurobiol & Anat Toledo OH 43614 USA Univ Calif Irvine Dept Psychobiol Irvine CA 92717 USA

Previously this laboratory demonstrated that forelimb removal at birth in rats results in the invasion of the cuneate nucleus by sciatic nerve axons and the development of cuneothalamic cells with receptive fields that include both the forelimb-stump and the hindlimb. However, unit-cluster recordings from primary somatosensory cortex (SI) of these animals revealed few sites in the forelimb-stump representation where responses to hindlimb stimulation also could be recorded. Recently we reported that hindlimb inputs to the SI forelimb-stump representation are suppressed functionally in neonatally amputated rats and that GABAergic inhibition is involved in this process. The present study was undertaken to assess the role that intracortical projections from the SI hindlimb representation may play in the functional reorganization of the SI forelimb-stump, field in these animals. The SI forelimb-stump representation was mapped during gamma-aminobutyric acid (GABA)-receptor blockade, both before and after electrolytic destruction of the SI hindlimb representation. Analysis of eight amputated rats showed that 75.8% of 264 stump recording sites possessed hindlimb receptive fields before destruction of the SI hindlimb. After the lesions, significantly fewer sites (13.2% of 197) were responsive to hindlimb stimulation (P < 0.0001). Electrolytic destruction of the SI lower-jaw representation in four additional control rats with neonatal forelimb amputation did not significantly reduce the percentage of hindlimb-responsive sites in the SI stump field during GABA-receptor blockade (P = 0.98). Similar results were obtained from three manipulated rats in which the SI hindlimb representation was silenced temporarily with a local cobalt chloride injection. Analysis of response latencies to sciatic nerve stimulation in the hindlimb and forelimb-stump representations suggested that the intracortical pathway(s) mediating the hindlimb responses in the forelimb-stump field may be polysyna

关键词：截肢术动物新生臂丛/生理学脑图钴/药理学电刺激前肢/生理学 GABA拮抗剂/药理学后肢/生理学颌/生理学幻肢/病理生理学反应时间/生理学坐骨神经/生理学躯体感觉皮质/药物作用躯体感觉皮质/生理学丘脑/生理学动物大鼠

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Cortically induced thalamic plasticity in the primate somatosensory system

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NATURE NEUROSCIENCE 1998年第3期1卷 226-229页

作者： Ergenzinger, ER Glasier, MM Hahm, JO Pons, TP Wake Forest Univ Sch Med Dept Neurosurg Winston Salem NC 27127 USA Wake Forest Univ Sch Med Program Neurosci Winston Salem NC 27127 USA Georgetown Univ Dept Neurosurg Washington DC 20057 USA

The influence of cortical feedback on receptive field organization in the thalamus was assessed in the primate somatosensory system. Chronic and acute suppression of neuronal activity in primary somatosensory cortex resulted in a striking enlargement of receptive fields in the ventroposterior thalamus. This finding demonstrates a dramatic 'top-down' influence of cortex on receptive field size in the somatosensory thalamus. In addition, this result has important implications for studies of adult neuronal plasticity because it indicates that changes in 'higher-order' areas of the brain can trigger extensive changes in the receptive field characteristics of neurons located earlier in the processing pathway.

关键词： 2-氨基-5-膦酰基戊酸盐/药理学兴奋性氨基酸拮抗剂/药理学反馈手/生理学恒河猴神经元可塑性/生理学神经元/药物作用神经元/生理学受体 N-甲基-D-天冬氨酸/拮抗剂和抑制剂躯体感觉皮质/细胞学躯体感觉皮质/药物作用躯体感觉皮质/生理学丘脑/细胞学丘脑/药物作用丘脑/生理学动物

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Neonatal lead exposure impairs development of rodent barrel field cortex

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2000年第10期97卷 5540-5545页

作者： Wilson, MA Johnston, MV Goldstein, GW Blue, ME Johns Hopkins Univ Kennedy Krieger Inst Baltimore MD 21205 USA Johns Hopkins Univ Dept Neurol Baltimore MD 21205 USA Johns Hopkins Univ Dept Pediat Baltimore MD 21205 USA Johns Hopkins Univ Dept Environm Hlth Sci Baltimore MD 21205 USA

Childhood exposure to low-level lead can permanently reduce intelligence, but the neurobiologic mechanism for this effect is unknown. We examined the impact of lead exposure on the development of cortical columns, using the rodent barrel field as a model. In all areas of mammalian neocortex, cortical columns constitute a fundamental structural unit subserving information processing. Barrel field cortex contains columnar processing units with distinct clusters of layer IV neurons that receive sensory input from individual whiskers. In this study, rat pups were exposed to 0, 0.2, 1, 1.5, or 2 g/liter lead acetate in their dam's drinking water from birth through postnatal day 10. This treatment, which coincides with the development of segregated columns in the barrel field, produced blood lead concentrations from 1 to 31 mu g/dl. On postnatal day 10, the area of the barrel field and of individual barrels was measured. A dose-related reduction in barrel field area was observed (Pearson correlation = -0.740;P < 0.001);mean barrel field area in the highest exposure group was decreased 12% Versus controls. individual barrels in the physiologically more active caudoventral group were affected preferentially Total cortical area measured in the same sections was not altered significantly by lead exposure. These data support the hypothesis that lead exposure may impair the development of columnar processing units in immature neocortex. We demonstrate that low levers of blood lead, in the range seen in many impoverished inner-city children, cause structural alterations in a neocortical somatosensory map.

关键词：投药口服动物新生剂量效应关系药物电子传递复合物Ⅳ/分析泌乳铅/血液铅中毒/病理生理学有机金属化合物/投药和剂量有机金属化合物/毒性大鼠 Long-Evans 大鼠 Sprague-Dawley 受体 AMPA/分析受体谷氨酸/分析受体亲代谢性谷氨酸盐/分析躯体感觉皮质/药物作用躯体感觉皮质/生长和发育躯体感觉皮质/病理学触须/神经支配动物女(雌)性大鼠

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Simultaneous reorganization in thalamocortical ensembles evolves over several hours after perioral capsaicin injections

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JOURNAL OF NEUROPHYSIOLOGY 1999年第2期82卷 963-977页

作者： Katz, DB Simon, SA Moody, A Nicolelis, MAL Duke Univ Med Ctr Dept Neurobiol Durham NC 27710 USA Univ N Carolina Dept Geog Chapel Hill NC 27599 USA

Reorganization of the somatosensory system was quantified by simultaneously recording from single-unit neural ensembles in the whisker regions of the ventral posterior medial (VPM) nucleus of the thalamus and the primary somatosensory (SI) cortex in anesthetized rats before, during, and after injecting capsaicin under the skin of the lip. Capsaicin, a compound that excites and then inactivates a subset of peripheral C and A delta fibers, triggered increases in spontaneous firing of thalamocortical neurons (10-15 min after injection), as well as rapid reorganization of the whisker representations in both the VPM and SI. During the first hour after capsaicin injection, 57% of the 139 recorded neurons either gained or lost at least one whisker response in their receptive fields (RFs). Capsaicin-related changes continued to emerge for greater than or equal to 6 h after the injection: Fifty percent of the single-neuron RFs changed between 1-2 and 5-6 h after capsaicin injection. Most (79%) of these late changes represented neural responses that had remained unchanged in the first postcapsaicin mapping;just under 20% of these late changes appeared in neurons that had previously shown no plasticity of response. The majority of the changes (55% immediately after injection, 66% 6 h later) involved "unmasking" of new tactile responses. RF change rates were comparable in SI and VPM (57-49%). Population analysis indicated that the reorganization was associated with a lessening of the "spatial coupling" between cortical neurons-a significant reduction in firing covariance that could be related to distances between neurons. This general loss of spatial coupling, in conjunction with increases in spontaneous firing, may create a situation that is favorable for the induction of synaptic plasticity. Our results indicate that the selective inactivation of a peripheral nociceptor subpopulation can induce rapid and long-evolving (greater than or equal to 6 h) shifts in the balance of in

关键词：方差分析辣椒辣素/药理学注射注射皮下多元分析神经元/药物作用大鼠 Long-Evans 躯体感觉皮质/药物作用丘脑/药物作用触须/神经支配动物女(雌)性大鼠

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The influence of single VB thalamocortical impulses on barrel columns of rabbit somatosensory cortex

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JOURNAL OF NEUROPHYSIOLOGY 2000年第5期83卷 2802-2813页

作者： Swadlow, HA Gusev, AG Univ Connecticut Dept Psychol Storrs CT 06269 USA Russian Acad Med Sci Moscow Brain Res Inst Moscow 103064 Russia

Extracellular recordings were obtained from single neurons in ventrobasal (VB) thalamus of awake rabbits while field potentials were recorded at various depths within topographically aligned and nonaligned barrel columns of somatosensory cortex (S1). Spike-triggered averages of cortical field potentials were obtained following action potentials in thalamic neurons. Action potentials in a VB neuron elicited a cortical response within layer 4 with three distinct components. 1) A biphasic, initially positive response (latency <1 ms) was interpreted to reflect activation of the VB axon terminals (the AxTP). This response was not affected by infusion of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist within the barrel. In contrast, later components of the response were completely eliminated and were interpreted to reflect focal synaptic potentials. 2) A negative potential [focal synaptic negativity (FSN)] occurred at a mean latency of 1.65 ms and lasted similar to 4 ms. This response had a rapid rise time (similar to 0.7 ms) and was interpreted to reflect monosynaptic excitation. 3) The third component was a positive potential (the FSP), with a slow rise time and a half-amplitude duration of similar to 30 ms. The FSP showed a weak reversal in superficial cortical layers and was interpreted to reflect di/polysynaptic inhibition. The amplitudes of the AxTP, the FSN, and the FSP reached a peak near layer 4 and were highly attenuated in both superficial and deep cortical layers. All components were attenuated or absent when the cortical electrode was missaligned from the thalamic electrode by a single cortical barrel. Deconvolution procedures revealed that the autocorrelogram of the presynaptic VB neuron had very little influence on either the amplitude or duration of the AxTP or the FSN, and only a minor influence (mean, 11%) on the amplitude of the FSP. We conclude that individual VB thalamic impulses entering a cortical barre

关键词：动作电位/生理学传入通路/生理学电刺激电极植入诱发电位/生理学兴奋性氨基酸拮抗剂/药理学新皮质/药物作用新皮质/生理学喹恶啉类/药理学反应时间/生理学躯体感觉皮质/药物作用躯体感觉皮质/生理学突触传递/生理学丘脑腹侧核/生理学触须/神经支配触须/生理学觉醒状态/生理学动物兔

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Impairments in prehension produced by early postnatal sensory motor cortex activity blockade

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JOURNAL OF NEUROPHYSIOLOGY 2000年第2期83卷 895-906页

作者： Martin, JH Donarummo, L Hacking, A Columbia Univ Ctr Neurobiol & Behav New York NY 10032 USA New York State Psychiat Inst & Hosp New York NY 10032 USA

Impairments in prehension produced by early postnatal sensory motor cortex activity blockade. J. Neurophysiol. 83: 895-906, 2000. This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion;age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching acid grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade b

关键词：年龄因素条件反射(心理学)/生理学关键期(心理学) 摄食行为/生理学前肢/生理学功能偏侧化/生理学 GABA激动剂/药理学运动皮质/药物作用运动皮质/生长和发育运动皮质/生理学运动技能/药物作用运动技能/生理学蝇蕈醇/药理学精神运动性行为/生理学躯体感觉皮质/药物作用躯体感觉皮质/生长和发育躯体感觉皮质/生理学空间知觉/生理学动物猫

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Serotonin depletion and barrel cortex development: Impact of growth impairment vs. serotonin effects on thalamocortical endings

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CEREBRAL CORTEX 2000年第2期10卷 181-191页

作者： Persico, AM Altamura, C Calia, E Puglisi-Allegra, S Ventura, R Lucchese, F Keller, F LUCBM Neurosci Lab Dept Physiol I-00155 Rome Italy LUCBM Serv Neurol I-00155 Rome Italy Univ Roma La Sapienza Dept Psychol Rome Italy

Converging evidence supports a role of serotonin (5-hydroxytryptamine;5-HT) in barrel cortex development. Systemic administration of 5-HT-depleting drugs reduces cross-sectional whisker barrel areas in the somatosensory cortex (SSC) of neonatal rats. Here we assess the relative impact on barrel pattern formation of (i) 5-HT depletion and (ii) decreased brain growth, which is often associated with pharmacological 5-HT depletion, by comparing the effects of 5-HT-depleting drugs with those of reduced protein intake. Left hemisphere 5-HT levels in the SSC and right hemisphere whisker barrel areas were assessed at postnatal day 6 (P6) in the same animal following injection of p-chloroamphetamine (PCA) or p-chlorophenylalanine (PCPA) at PO. Both drugs significantly reduced cortical 5-HT content and mean barrel areas at P6, but also body and brain growth. Differences in brain weight accounted for 84.4 % of the variance in barrel size, with negligible contributions by cortical 5-HT content. PCPA-treated animals sacrificed at P14 yielded similar trends, albeit less pronounced. Finally, reduced protein intake resulted in lower body weight and cortical 5-HT levels at P6, but yielded no change in brain weight or mean barrel area. Barrel formation therefore appears markedly less sensitive to 5-HT depletion per se than to drug-induced growth impairment.

关键词：衰老动物新生体重/药物作用脑/解剖学和组织学芬克洛宁/药理学羟基吲哚乙酸/代谢器官测量/药物作用大鼠近交Lew 血清素/代谢躯体感觉皮质/药物作用躯体感觉皮质/生长和发育躯体感觉皮质/生理学触须/神经支配 p-氯苯丙胺/药理学动物大鼠

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Prenatal exposure to toluene results in abnormal neurogenesis and migration in rat somatosensory cortex

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PEDIATRIC RESEARCH 2000年第3期47卷 362-368页

作者： Gospe, SM Zhou, SS Univ Calif Davis Sect Child Neurol Dept Neurol Davis CA 95616 USA Univ Calif Davis Sect Child Neurol Dept Pediat Davis CA 95616 USA

Toluene inhalant abuse during pregnancy may result in growth-retarded microcephalic newborns who subsequently demonstrate developmental impairment. By using a rat model of toluene-abuse embryopathy, we studied the effects of prenatal toluene exposure on the generation and migration of cortical neurons. Dams were exposed by gavage to either corn oil or toluene diluted in corn oil on d 6-21 of gestation. The time of origin of cortical neurons was determined in the mature pups of dams injected with the thymidine analogue 5'-bromodeoxyuridine on 1 d during the period from d 13-21 of gestation. 5'-Bromodeoxyuridine-labeled neurons were identified by immunohistochemistry in a 400-mu m-wide column of somatosensory cortex. The brains of the toluene-exposed pups had a significant reduction in the number of neurons within each cortical layer (p < 0.001). Depending on the cortical layer, the generation of neurons in the toluene-exposed pups was delayed by 1 or 2 d. In addition, the brains of the toluene-exposed pups also showed evidence of abnormal neuronal migration. However, there were no differences in either brain weight or body weight between the control and toluene-exposed pups. These observations suggest that although prenatal toluene exposure results in abnormal neuronal proliferation and migration, brain weight in the toluene-exposed pups may be preserved by enhanced development of glia or the neuropil.

关键词：大鼠 Sprague-Dawley 躯体感觉皮质/药物作用躯体感觉皮质/胚胎学躯体感觉皮质/病理学致畸剂甲苯/投药和剂量甲苯/毒性动物女(雌)性妊娠大鼠

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Immediate thalamic sensory plasticity depends on corticothalamic feedback

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1999年第14期96卷 8200-8205页

作者： Krupa, DJ Ghazanfar, AA Nicolelis, MAL Duke Univ Med Ctr Dept Neurobiol Durham NC 27710 USA

Multiple neuron ensemble recordings were obtained simultaneously from both the primary somatosensory (SI) cortex and the ventroposterior medial thalamus (VPM) before and during the combined administration of reversible inactivation of the SI cortex and a reversible subcutaneous block of peripheral trigeminal nerve fibers. This procedure was performed to quantify the contribution of descending corticofugal projections on (i) the normal organization of thalamic somatosensory receptive fields and (ii) the thalamic somatosensory plastic reorganization that immediately follows a peripheral deafferentation. Reversible inactivation of SI cortex resulted in immediate changes in receptive field properties throughout the VPM. Cortical inactivation also significantly reduced but did not completely eliminate the occurrence of WM receptive field reorganization resulting from the reversible peripheral deafferentation. This result suggests that the thalamic plasticity that is seen immediately after a peripheral deafferentation is dependent upon both descending-corticofugal projections and ascending trigeminothalamic projections.

关键词：脑图电刺激输注胃肠外利多卡因/药理学蝇蕈醇/投药和剂量蝇蕈醇/药理学神经纤维/生理学神经通路/药物作用神经通路/生理学神经元可塑性神经元/生理学大鼠 Long-Evans 躯体感觉皮质/药物作用躯体感觉皮质/生理学丘脑/生理学时间因素三叉神经/生理学触须/神经支配动物女(雌)性大鼠

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