Neural Oscillations and Multisensory Processing.

Neural oscillations play a role in sensory processing by coordinating synchronized neuronal activity. Synchronization of gamma oscillations is engaged in local computation of feedforward signals and synchronization of alpha-beta oscillations is engaged in feedback processing over long-range areas. These spatially and spectrally segregated bi-directional signals may be integrated by a mechanism of cross-frequency coupling. Synchronization of neural oscillations has also been proposed as a mechanism for information integration across multiple sensory modalities. A transient stimulus or rhythmic stimulus from one modality may lead to phase alignment of ongoing neural oscillations in multiple sensory cortices, through a mechanism of cross-modal phase reset or cross-modal neural entrainment. Synchronized activities in multiple sensory cortices are more likely to boost stronger activities in downstream areas. Compared to synchronized oscillations, asynchronized oscillations may impede signal processing, and may contribute to sensory selection by setting the oscillations in the target-related cortex and the oscillations in the distractor-related cortex to opposite phases.

Spike Phase Shift Relative to Beta Oscillations Mediates Modality Selection.

How does the brain selectively process signals from stimuli of different modalities? Coherent oscillations may function in coordinating communication between neuronal populations simultaneously involved in such cognitive behavior. Beta power (12-30 Hz) is implicated in top-down cognitive processes. Here we test the hypothesis that the brain increases encoding and behavioral influence of a target modality by shifting the relationship of neuronal spike phases relative to beta oscillations between primary sensory cortices and higher cortices. We simultaneously recorded neuronal spike and local field potentials in the posterior parietal cortex (PPC) and the primary auditory cortex (A1) when male rats made choices to either auditory or visual stimuli. Neuronal spikes exhibited modality-related phase locking to beta oscillations during stimulus sampling, and the phase shift between neuronal subpopulations demonstrated faster top-down signaling from PPC to A1 neurons when animals attended to auditory rather than visual stimuli. Importantly, complementary to spike timing, spike phase predicted rats' attended-to target in single trials, which was related to the animals' performance. Our findings support a candidate mechanism that cortices encode targets from different modalities by shifting neuronal spike phase. This work may extend our understanding of the importance of spike phase as a coding and readout mechanism.

Cocaine-induced impulsive choices are accompanied by impaired delay-dependent anticipatory activity in basolateral amygdala.

Addicts and drug-experienced animals have decision-making deficits in delayed reinforcement choice task, in which they prefer small immediate rewards over large delayed rewards. Here, we show evidence that this deficit is accompanied by changed coding of delay length in the basolateral amygdala (BLA). A subset of neurons in BLA demonstrated delay-dependent anticipatory activity (either increase or decrease as a function of delay to reward) in naive rats. After 30 days of withdrawal from chronic cocaine treatment (30 mg/kg/day for 10 days ip), the proportion of delay-dependent anticipatory neurons reduced, whereas delay-dependent activity in response to elapsed delay after reward delivery increased, both in the proportion of delay-dependent neurons and in the extent of delay dependence. Cocaine exposure increased, instead of decreased, BLA neuronal expectation for different reward magnitudes. These results indicate that BLA is critical for representing and maintaining the information of delayed reward before its delivery, and cocaine exposure may affect decision-making by impairing perception of delay instead of the ability to assess the differences in reward size.

Rats Generate Vibrissal Sensory Evidence until Boundary Crossing Triggers a Decision.

Behaviors in which primates collect externally generated streams of sensory evidence, such as judgment of random dot motion direction, are explained by a bounded integration decision model. Does this model extend to rodents, and does it account for behavior in which the motor system generates evidence through interactions with the environment? In this study, rats palpated surfaces to identify the texture before them, showing marked trial-to-trial variability in the number of touches prior to expressing their choice. By high-speed video, we tracked whisker kinematic features and characterized how they encoded the contacted texture. Next, we quantified the evidence for each candidate texture transmitted on each touch by the specified whisker kinematic features. The instant of choice was well fit by modeling the brain as an integrator that gives the greatest weight to vibrissal evidence on first touch and exponentially less weight to evidence on successive touches; according to this model, the rat makes a decision when the accumulated quantity of evidence for one texture reaches a boundary. In summary, evidence appears to be accumulated within the brain until sufficient to support a well-grounded choice. These findings extend the framework of bounded sensory integration from primates to rodents and from passively received evidence to evidence that is actively generated by the sensorimotor system.

Texture Identification by Bounded Integration of Sensory Cortical Signals.

Recent work demonstrated that when a rat palpates a surface to identify its texture, signals generated by whisker kinematics are integrated by the brain, one touch at a time, until the accumulated evidence supports a well-grounded choice. The framework of decision making through bounded integration, previously attributed to primates, thus extends to rodents. In the present study, we ask whether vibrissal somatosensory cortex (vS1 and vS2) functions as the integrator of incoming evidence or, alternatively, as a relay of evidence to a downstream integrator. Rats carried out 1-6 touches per trial to discriminate among candidate textures. We calculated the evidence for each texture, per touch, carried by the firing rates of sets of neurons in vS1 and vS2. The quantity of information within vS1 and vS2 did not grow progressively; instead, the decision was accounted for by modeling a downstream integrator that accumulated packets of vS1 and vS2 texture information until the total quantity of evidence for one texture reached a boundary. In this behavioral task, vibrissal somatosensory cortex appears to act as a sensory relay. Bounded integration is likely to take place in regions targeted by somatosensory cortex.

Biochemical pathways in the antiatherosclerotic effect of berberine.

BACKGROUND: This study investigated the inhibitory effect of berberine (BBR) on lipopolysaccharide (LPS) induced cyclooxygenase-2 (COX-2) expression via the mitogen activated protein kinase (MAPK) signalling cascade pathways in human peripheral blood monocytes (PBMC). METHODS: PBMC from whole blood were isolated and cultured for up to 24 hours after division into 5 groups treated with LPS, LPS + BBR 25 micromol/L, LPS + BBR 50 micromol/L or LPS + BBR 100 micromol/L and untreated. Monocytes were extracted for RT-PCR and Western blot analyses to examine COX-2 mRNA and protein activated expression of p38 mitogen activated protein kinase (p38MAPK), Jun N-terminal kinase (JNK) and extracellular regulated kinases 1/2 (ERK1/2) signalling pathways. RESULTS: COX-2 mRNA and protein expression decreased to a minimum at 12 hours after BBR treatment (P < 0.05). With the increasing concentration of BBR treatment, the COX-2 expression decreased progressively (P < 0.01). With BBR treatment for 6, 12 or 24 hours at three doses, ERK1/2 protein expression was significantly inhibited. For the JNK pathway, only with the treatment of BBR at the concentration of 100 micromol/L was JNK protein expression inhibited compared with the LPS stimulation group (P < 0.01). Irrespective of the BBR concentration, no difference was shown between the BBR group and the LPS group for p38MAPK protein expression. Human monocytes COX-2 mRNA, by RT-PCR, and protein expression, by Western blot analysis, were inhibited when incubated with PD98059, SP600125 and SB203580 (P < 0.05). CONCLUSIONS: Berberine inhibits COX-2 expression via the ERK1/2 signalling pathway and, possibly, at a high dosage via the JNK pathway. P38MAPK may have no relationship with the effect of BBR in PBMC. Berberine inhibited COX-2 mRNA and protein expression in a dose dependent manner and suppressed COX-2 expression to a minimal level after 12 hours of berberine treatment.

Peripheral electrical stimulation reversed the cell size reduction and increased BDNF level in the ventral tegmental area in chronic morphine-treated rats.

Chronic morphine administration induces functional and morphological alterations in the mesolimbic dopamine system (MLDS), which is believed to be the neurobiological substrate of opiate addiction. Our previous studies have demonstrated that peripheral electrical stimulation (PES) can suppress morphine withdrawal syndrome and morphine-induced conditioned place preference (CPP) in rats. The present study was designed to investigate if PES could reverse the cell size reduction induced by chronic morphine treatment in the ventral tegmental area (VTA), which is an important area of the MLDS. Immunohistochemical observations showed that the cell size of dopaminergic neurons in the VTA reduced significantly in the chronic morphine-treated rats with a concomitant decrease in the number of BDNF-positive cells compared to the saline-treated rats. A much milder morphological change, accompanying with an increased number of BDNF-positive cells, was observed in dopaminergic neurons in the rats that received repeated 100 Hz PES after morphine withdrawal. In another experiment, enzyme-linked immunosorbent assay (ELISA) reconfirmed a significant up-regulation of BDNF protein level in the VTA in the rats received 100 Hz PES after morphine abstinence. These results indicate that PES could facilitate the morphological recovery of the VTA dopaminergic cells damaged by chronic morphine treatment and up-regulate the BDNF protein level in the VTA. Activation of endogenous BDNF by PES may play a role in the recovery of the injured dopaminergic neurons in the morphine addictive rats.

A comparison between spontaneous electroencephalographic activities induced by morphine and morphine-related environment in rats.

Previous studies demonstrated that drug cues could elicit drug-like or withdrawal-like effect, both subjectively and physiologically. However, few studies have compared the central activities induced by a drug-related environment and the drug itself. The aim of this study was to observe and compare electroencephalographic (EEG) changes induced by acute morphine administration and by the morphine-related environment. EEG activities were recorded via twelve skull electrodes scattered on the left and right cortex in conscious, freely moving rats, either after acute morphine administration or after successful training of conditioned place preference. Acute administration of morphine (0.1, 0.5, 1, 5, 10, 20 mg/kg, i.p.) produced an increase in absolute EEG power in the delta, theta, alpha1, alpha2, beta1, and beta2 bands, as well as a decrease in the gamma band. Topographic mapping revealed a maximal increase in the lateral leads in the theta band and a maximal change in the centro-frontal region in the remaining bands. After place conditioning training, the morphine-related environment induced a diffuse decrease in absolute power in the delta, theta, alpha1, alpha2, beta1, and beta2 bands, which was opposite to the changes induced by acute morphine administration. In addition, the changes in relative power induced by the two situations also diverged. These results indicate that the central mechanisms underlying the motivation of morphine-induced place preference may be somehow different from those underlying the reward effects produced by acute morphine administration.

Persistent Neuronal Activity in Anterior Cingulate Cortex Correlates with Sustained Attention in Rats Regardless of Sensory Modality.

The anterior cingulate cortex (ACC) has long been thought to regulate conflict between an object of attention and distractors during goal-directed sustained attention. However, it is unclear whether ACC serves to sustained attention itself. Here, we developed a task in which the time course of sustained attention could be controlled in rats. Then, using pharmacological lesion experiments, we employed it to assess function of ACC in sustained attention. We then recorded neuronal activity in ACC using multichannel extracellular recording techniques and identified specific ACC neurons persistently activated during the period of attention. Further experiments showed that target modality had minimal influence on the neuronal activity, and distracting external sensory input during the attention period did not perturb persistent neuronal activity. Additionally, minimal trial-to-trial variability in neuronal activity observed during sustained attention supports a role for ACC neurons in that behavior. Therefore, we conclude that the ACC neuronal activity correlates with sustained attention.

The possible involvement of endogenous ligands for mu-, delta- and kappa-opioid receptors in modulating morphine-induced CPP expression in rats.

Previous studies suggested that electroacupuncture (EA) can suppress opioid dependence by the release of endogenous opioid peptides. To explore the site of action and the receptors involved, we tried to inject highly specific agonists for mu-, delta- and kappa-opioid receptors into the CNS to test whether it can suppress morphine-induced conditioned place preference (CPP) in the rat. Male Sprague-Dawley rats were trained with 4 mg/kg morphine, i.p. for 4 days to establish the CPP model. This CPP can be prevented by (a) i.p. injection of 3 mg/kg dose of morphine, (b) intracerebroventricular (i.c.v.) injection of micrograms doses of the selective mu-opioid receptor agonist DAMGO, delta-agonist DPDPE or kappa-agonist U-50,488H or (c) microinjection of DAMGO, DPDPE or U50488H into the shell of the nucleus accumbens (NAc). The results suggest that the release of endogenous mu-, delta- and kappa-opioid agonists in the NAc shell may play a role for EA suppression of opiate addiction.

Meta-analysis of defibrase in treatment of acute cerebral infarction.

BACKGROUND: Fibrinogen-depleting agents are promising in the treatment of cerebral ischemic disease. They were studied by many trials, and the outcomes were different because of different regimens and different doses. In this study, we assessed the efficacy and safety of defibrase on acute cerebral infarction in China. METHODS: A search using Chinese hospital knowledge database (CHKD) and MEDLINE database for randomized controlled trials was carried out. A CHKD (1994 June 2005) search was performed with the keyword "defibrase", then a second search for the keyword "acute cerebral infarction"; a MEDLINE search (1950 June 2005) was performed with the following keywords: [(cerebral ischemia), OR (acute cerebral infarction), OR (stroke)], AND [defibrase]. Meta-analysis was performed with RevMan software 4.2. RESULTS: Included were 14 studies comparing the efficiency and safety of defibrase with other drugs in the treatment of acute cerebral infarction. Patients' records were pooled (total 646 patients; defibrase, n = 328, no defibrase n = 318). Neurological deficit score (NDS) before treatment showed weighted mean differences (WMD) = 0.95, 95% confidence interval (CI) = (-0.60, 2.50), P = 0.23; NDS after treatment showed WMD = -2.20, 95% CI = (-4.21, -0.18), P = 0.03; Barthel index at 3 months showed WMD = 4.45, 95% CI = (-0.13, 9.03), P = 0.06; the plasma fibrinogen level before treatment showed WMD = 0.02, 95% CI = (-0.16, 0.19), P = 0.86; plasma fibrinogen level after treatment showed WMD = -1.51, 95% CI = (-1.88, -1.15), P < 0.00 001. CONCLUSIONS: With the given dose and regimen of defibrase in China, defibrase may play a role of anticoagulation. It might inhibit the progression of stroke and prevent the recurrence of stroke.

Effects of aspirin on atherosclerosis and the cyclooxygenase-2 expression in atherosclerotic rabbits.

BACKGROUND: Atherosclerosis is a complex vascular inflammatory disease. Aspirin is a mainstay in the prevention of vascular complications of atherosclerosis. In this study, the effectiveness of aspirin in suppressing atherosclerosis and the inflammation process was evaluated in rabbits fed with a high fat diet. METHODS: Eighteen male New Zealand rabbits were randomly divided into 3 groups: control group, untreated cholesterol-fed group, aspirin treated cholesterol-fed group, which were fed for 12 weeks. After 12 weeks, the aorta was harvested for pathologic morphology observation. Immunohistochemical analysis of cyclooxygenase-2 (COX-2), macrophage and vascular smooth muscle cell (VSMC) was performed. The statistical analysis was performed by the statistical program SPSS10.0. RESULTS: The aorta plaque/intima size (P/I) by pathologic morphology observation was 0%, (59.6 +/- 13.7)% and (36.3 +/- 16.5)% in the control, untreated cholesterol-fed group and aspirin treated group, respectively. The maximum plaque thickness, the degree of artery stenosis and the proportion of the intimal circumference occupied by atheroma of the 3 groups were significantly different from each other (P < 0.01). The expression of COX-2 and macrophage in plaque of the aspirin treated group were decreased compared with that in untreated cholesterol-fed group. However, no difference was found in the expression of VSMC between the aspirin treated and the untreated cholesterol-fed group. CONCLUSION: The mechanism of atherosclerosis suppression by aspirin in cholesterol-fed rabbits is related to the inhibition of COX-2 expression together with the reduced inflammation followed by, but not related to the hypolipidemic effects.

[Processing of spatial information by hippocampal place cells].

Hippocampal place cells can process the environmental inputs and make up a cognitive map in the hippocampus, or strengthen the synaptic connections within an association cortical cell assembly,thus creating a permanent engram for a spatial site. Outputs from the hippocampus are then integrated with other inputs within the nucleus accumbens and finally initiate a goal-directed behavior through the motor circuit.

Role of basolateral amygdala dopamine D2 receptors in impulsive choice in acute cocaine-treated rats.

Psychostimulant substances have been found to either increase or inhibit impulsive choice (preference to choose small immediate reward over large delayed reward) in laboratory animals. Although central dopamine transmission has been demonstrated to be involved in impulsivity and drug addiction, little is known regarding dopaminergic neurotransmission in addictive drug-induced alteration of impulse control. In this study, we used a delay discounting model to measure impulsive choice in rats and found that acute cocaine dose-dependently decreased impulsive choice in rats. Intraperitoneal injection (i.p.) of D1 receptor antagonist SCH23390 (0.02 mg/kg) could increase the impulsive choice but had no effect on the inhibition of impulsive choice induced by acute cocaine exposure. D2 receptor antagonist eticlopride (0.06 mg/kg) had no effect on the choice behavior itself, but it reversed acute cocaine-induced impulse inhibition. Moreover, bilateral microinjection of eticlopride (1 µg/side) into the basolateral amygdala (BLA) but not the nucleus accumbens (NAc) core reversed the inhibitory effect of acute cocaine on impulsive choice. These data suggest important but dissociable roles of dopamine D1 and D2 receptors in impulse control. The preference of delayed rewards depends on D1 receptors, whereas acute cocaine inhibited impulsive choice by activating D2 receptors in the BLA.

Complementary contributions of spike timing and spike rate to perceptual decisions in rat S1 and S2 cortex.

When a neuron responds to a sensory stimulus, two fundamental codes [1-6] may transmit the information specifying stimulus identity--spike rate (the total number of spikes in the sequence, normalized by time) and spike timing (the detailed millisecond-scale temporal structure of the response). To assess the functional significance of these codes, we recorded neuronal responses in primary (S1) and secondary (S2) somatosensory cortex of five rats as they used their whiskers to identify textured surfaces. From the spike trains evoked during whisker contact with the texture, we computed the information that rate and timing codes carried about texture identity and about the rat's choice. S1 and S2 spike timing carried more information about stimulus and about choice than spike rates; the conjunction of rate and timing carried more information than either code alone. Moreover, on trials when our spike-timing-decoding algorithm extracted faithful texture information, the rat was more likely to choose correctly; when our spike-timing-decoding algorithm extracted misleading texture information, the rat was more likely to err. For spike rate information, the relationship between faithfulness of the message and correct choice was significant but weaker. These results indicate that spike timing makes crucial contributions to tactile perception, complementing and surpassing those made by rate. The language by which somatosensory cortical neurons transmit information, and the readout mechanism used to produce behavior, appears to rely on multiplexed signals from spike rate and timing.

Whisking and whisker kinematics during a texture classification task.

Rats explore objects by rhythmically whisking with their vibrissae. The goal of the present study is to learn more about the motor output used by rats to acquire texture information as well as the whisker motion evoked by texture contact. We trained four rats to discriminate between different grooved textures and used high-speed video to characterize whisker motion during the task. The variance in whisking parameters among subjects was notable. After whisker trimming, the animals changed their behaviour in ways that appear consistent with an optimization of whisker movement to compensate for lost information. These results lead to the intriguing notion that the rats use an information-seeking 'cognitive' motor strategy, instead of a rigid motor programme. Distinct stick/slip events occurred during texture palpation and their frequency increased in relation to the spatial frequency of the grooves. The results allow a preliminary assessment of three candidate texture-coding mechanisms-the number of grooves encountered during each touch, the temporal difference between groove contacts and the spatial pattern of groove contacts across the whiskers.

[Effect of ileocecum interposition graft as pylorus replacement on glycometabolism].

OBJECTIVE: To evaluate the application of ileocecum interposition (ii) graft as pylorus replacement in alimentary reconstruction. METHODS: Twenty- one minipigs were randomly divided into three groups: sham operation group (control group), B - i group and ii group. The levels of blood glucose were measured by quick blood glucose testing of paper at 0, 30, 60, 90, and 120 minutes of oral glucose after 60 and 120 post- operative days to compare gastric emptying of liquid feeds. RESULTS: Two months after operation,the peak of blood glucose was (7.8+/- 1.0)mmol/ L, (7.1+/- 0.8)mmol/ L, (4.1+/- 0.4)mmol/ L in B - i, ii group and control group respectively, there were significant differences between the two operation groups and control group (P< 0.01). Four months after operation, the peak of blood glucose was (6.9+/- 1.0) mmol/ L, (5.2+/- 0.8)mmol/ L, (4.2+/- 0.5)mmol/ L, respectively, there was no significant difference between ii group and control group (P > 0.05),but there were significant differences between both of the above two groups and B - i group (P< 0.01). CONCLUSION: The ileocecum interposition graft can offer specific advantages over current reconstruction procedures.