Enhanced excitability of thalamic sensory neurons and slow-wave EEG pattern after stimuli that induce spinal long-term potentiation.

Spinal nociceptive neurons are well known to undergo a process of long-term potentiation (LTP) following conditioning by high-frequency sciatic nerve stimulation (HFS) at intensities recruiting C-fibers. However, little if any information exists as to whether such HFS conditioning that produces spinal LTP affects sensory transmission at supraspinal levels. The present study explored this possibility. Conventional extracellular recording methods were used to examine the consequences of HFS versus sham HFS conditioning on individual wide-dynamic range thalamic neurons located in the ventro-postero-lateral (VPL) nucleus in isoflurane-anesthetized rats. Following HFS, the ongoing firing rate and stimulus-evoked (brush, pinch, sciatic nerve) responses were markedly enhanced as were responses to juxtacellular, microiontophoretic applications of glutamate. These HFS-induced enhancements lasted throughout the recording period. Sham stimuli had no effect on VPL neuron excitability. Cortical electroencephalographic (EEG) wave activities were also measured around HFS in conjunction with VPL neuron recordings. The cortical EEG pattern under baseline conditions consisted of recurring short duration bursts of high-amplitude slow waves followed by longer periods of flat EEG. Following HFS, the EEG shifted to a continuous large-amplitude, slow-wave pattern within the 0.5-8.0 Hz bandwidth lasting throughout the recording period. Sham HFS did not alter EEG activity. Sciatic nerve conditioning at A-δ fiber strength, known to reverse spinal LTP, did not alter enhanced neuronal excitability or the EEG slow-wave pattern induced by HFS. These data support the concept that HFS conditioning of the sciatic nerve, which leads to spinal LTP, is associated with distinct, long-lasting changes in the excitability of neurons comprising thalamocortical networks.

Bacopa monnieri increases cerebral blood flow in rat independent of blood pressure.

Bacopa monnieri (L.) Wettst. (Brahmi in India and Thailand) is an ayurvedic dementia treatment, but its effect on cerebral blood flow (CBF) is still unknown. We sought to test its chronic and acute effects on CBF compared with Ginkgo biloba and donepezil. CBF was measured by laser Doppler from rat cerebral cortex after 8 weeks of daily oral dosing of these drugs. Systolic blood pressure was also measured using the tail cuff method or via arterial cannulation. In rats treated with B. monnieri (40 mg/kg), CBF was 25% increased [2927 ± 123 perfusion units, (PU)] compared with shams (2337 ± 217 PU, p < 0.05, nine rats). G. biloba (60 mg/kg) also increased CBF (by 29% to 3019 ± 208 PU, p < 0.05, nine rats). No clear effect was obtained with donepezil (1 mg/kg). Chronic administration of the preparations had no effect on blood pressure. In contrast, intravenous acute infusion of these herbals (20-60 mg/kg) had marked dose-dependent hypotensive actions (diastolic ~31 mmHg lower with 40 mg/kg of either extract), which correspondingly reduced CBF by ~15%. Likewise, CBF fell slightly with acute intravenous sodium nitroprusside and rose with noradrenaline. Donepezil (1 mg/kg) was slightly hypotensive without affecting CBF. Increased CBF with B. monnieri may account for its reported procognitive effect, and its further exploration as an alternative nootropic drug is worthwhile.

The effects of Tabernaemontana divaricata root extract on amyloid beta-peptide 25-35 peptides induced cognitive deficits in mice.

UNLABELLED: ETHNOPHAMACOLOGICAL RELEVANCE: Tabernaemontana divaricata (TD), a Thai medicinal herb, has been widely used as an analgesic, sedative, or a cough syrup. Moreover, it has been used in traditional rejuvenation remedies as for preventing forgetfulness and improving the memory. AIM OF STUDY: The present study aimed to determine the effect of TD on Abeta25-35 peptides induced cognitive deficits and acetylcholinesterase activity in mice. MATERIALS AND METHODS: Mice were pretreated with TDE (250, 500 and 1,000 mg/kg body weight) for 28 days and then received i.c.v. injection of Abeta25-35 peptides. Cognitive performance was evaluated using the Morris water maze (MWM) and step-down avoidance test. The Ellman's colorimetric method was used to investigate the levels of cortical and hippocampal AChE activity. RESULTS: Abeta25-35 peptides induced the memory impairment and the increased levels of cortical and hippocampal AChE activity. The consumption of TDE significantly improved the memory impairment and attenuated the brain levels of AChE activity induced by Abeta25-35 peptides. CONCLUSIONS: These findings suggest that subchronic administration of TDE might prevent the Abeta25-35 peptides induced memory deficits by decreasing the AChE activity level. Therefore TDE could potentially be one of nootropic supplements for those elderly people suffering from dementia such as the AD patients.

Network actions of pentobarbital in the rat mesopontine tegmentum on sensory inflow through the spinothalamic tract.

The recent discovery of a barbiturate-sensitive "general anesthesia switch" mechanism localized in the rat brain stem mesopontine tegmental anesthesia area (MPTA) has challenged the current view of the nonspecific actions of general anesthetic agents in the CNS. In this study we provide electrophysiological evidence that the antinociception, which accompanies the behavioral state resembling general anesthesia following pentobarbital (PB) microinjections into the MPTA of awake rats, could be accompanied by the attenuation of sensory transmission through the spinothalamic tract (STT). Following bilateral microinjections of PB into the MPTA spontaneous firing rate (SFR), antidromic firing index (FI), and sciatic (Sc) as well as sural (Su) nerve-evoked responses (ER) of identified lumbar STT neurons in the isoflurane-anesthetized rat were quantified using extracellular recording techniques. Microinjections of PB into the MPTA significantly suppressed the SFR (47%), magnitudes of Sc- (26%) and Su-ER (36%), and FI (41%) of STT neurons. Microinjections of PB-free vehicle control did not alter any of the above-cited electrophysiological parameters. The results from this study suggest that antinociception, which occurs during the anesthesia-like state following PB microinjections into the MPTA, may be due, in part, to (in)direct inhibition of STT neurons via switching mechanism(s) located in the MPTA. This study provides a provenance for investigating electrophysiologically the actions on STT neurons of other current agents used clinically to maintain the state of general anesthesia.

State-dependent GABAergic inhibition of sciatic nerve-evoked responses of dorsal spinocerebellar tract neurons.

Peripheral nerve-evoked potentials recorded in the cerebellum 35 yr ago inferred that sensory transmission via the dorsal spinocerebellar tract (DSCT) is reduced occasionally and only during eye movements of active sleep compared with wakefulness or quiet sleep. A reduction or withdrawal of primary afferent input and/or ongoing inhibition of individual lumbar DSCT neurons may underlie this occurrence. This study distinguished between these possibilities by examining whether peripheral nerve-evoked responses recorded from individual DSCT neurons are suppressed specifically during active sleep, and if so, whether GABA mediates this phenomenon. Synaptic responses to threshold stimuli applied to the sciatic nerve were characterized by a single spike response at short latency and/or a longer latency burst of action potentials. During the state of quiet wakefulness, response magnitude did not differ from that observed during quiet sleep. During active sleep, short and long latency responses were suppressed by 26 and 14%, respectively, and returned to pre-active sleep levels following awakening from active sleep. Sciatic nerve-evoked early and late responses were further analyzed in a paired fashion around computer-tagged eye movement events that hallmark the state of active sleep. Response magnitude was suppressed by 14.4 and 11.5%, respectively, during eye movement events of active sleep. The GABA(A) antagonist bicuculline, applied juxtacellularly by microiontophoresis, abolished response suppression during non-eye movement periods and eye movement events of active sleep. In conclusion, synaptic transmission via DSCT neurons is inhibited by GABA tonically during non-eye movement periods and phasically during eye movement events of active sleep.

Transmission through the dorsal spinocerebellar and spinoreticular tracts: wakefulness versus thiopental anesthesia.

BACKGROUND: Most of what is known regarding the actions of injectable barbiturate anesthetics on the activity of lumbar sensory neurons arises from experiments performed in acute animal preparations that are exposed to invasive surgery and neural depression caused by coadministered inhalational anesthetics. Other parameters such as cortical synchronization and motor ouflow are typically not monitored, and, therefore, anesthetic actions on multiple cellular systems have not been quantitatively compared. METHODS: The activities of antidromically identified dorsal spinocerebellar and spinoreticular tract neurons, neck motoneurons, and cortical neurons were monitored extracellularly before, during, and following recovery from the anesthetic state induced by thiopental in intact, chronically instrumented animal preparations. RESULTS: Intravenous administration of 15 mg/kg, but not 5 mg/kg, of thiopental to awake cats induced general anesthesia that was characterized by 5-10 min of cortical synchronization, reflected as large-amplitude slow-wave events and neck muscle atonia. However, even though the animal behaviorally began to reemerge from the anesthetic state after this 5-10-min period, neck muscle (neck motoneuron) activity recovered more slowly and remained significantly suppressed for up to 23 min after thiopental administration. The spontaneous activity of both dorsal spinocerebellar and spinoreticular tract neurons was maximally suppressed 5 min after administration but remained significantly attenuated for up to 17 min after injection. Peripheral nerve and glutamate-evoked responses of dorsal spinocerebellar and spinoreticular tract neurons were particularly sensitive to thiopental administration and remained suppressed for up to 20 min after injection. CONCLUSIONS: These results demonstrate that thiopental administration is associated with a prolonged blockade of motoneuron output and sensory transmission through the dorsal spinocerebellar and spinoreticular tracts that exceeds the duration of general anesthesia. Further, the blockade of glutamate-evoked neuronal responses indicates that these effects are due, in part, to a local action of the drug in the spinal cord. The authors suggest that this combination of lumbar sensory and motoneuron inhibition underlies the prolonged impairment of reflex coordination observed when thiopental is used clinically.

State-related inhibition by GABA and glycine of transmission in Clarke's column.

During the state of active sleep (AS), Clarke's column dorsal spinocerebellar tract (DSCT) neurons undergo a marked reduction in their spontaneous and excitatory amino acid (EAA)-evoked responses. The present study was performed to examine the magnitude, consistency of AS-specific suppression, and potential role of classical inhibitory amino acids GABA and glycine (GLY) in mediating this phenomenon. AS-specific suppression of DSCT neurons, expressed as the reduction in mean spontaneous firing rate during AS versus the preceding episode of wakefulness, was compared across three consecutive sleep cycles (SC), each consisting of wakefulness (W), AS, and awakening from AS (RW). Spontaneous spike rate did not differ during W or RW between SC1, SC2, and SC3. AS-specific suppression of spontaneous firing rate was found to be consistent and measured 40.3, 31.5, and 41.6% in SC1, SC2, and SC3, respectively, indicating that such inhibition is marked and stable for pharmacological analyses. Microiontophoretic experiments were performed in which the magnitude of AS-specific suppression of spontaneous spike activity was measured over three consecutive SCs: SC1-control (no drug), SC2-test (drug), and SC3-recovery (no drug). The magnitude of AS-specific suppression during SC2-test measured only 11.7 or 14.6% in the presence of GABA(A) antagonist bicuculline (BIC) or GLY antagonist strychnine (STY), respectively. Coadministration of BIC and STY abolished AS-specific suppression. AS-specific suppression of EAA-evoked DSCT spike activity was also abolished in SC2-test after BIC or STY, respectively. We conclude that GABA and GLY mediate behavioral state-specific inhibition of ascending sensory transmission via Clarke's column DSCT neurons.