[Correlation between theta-gamma neural oscillations in hippocampal CA3 area and the spatial identifying and cognitive ability in rats].

The present study was aimed to explore the correlation between θ-γ neural oscillations phase-amplitude coupling (PAC) in hippocampal CA3 area and the changes of spatial identifying and cognitive ability before and after shock avoidance training in rats. According to the results of Y-type maze shock avoidance training, the rats were divided into two groups: the fast avoidance response group and the general avoidance response group. The local field potential (LFP) of hippocampal CA3 area was recorded by wireless telemetry before and after shock avoidance training. The variation of θ oscillation (3-7 Hz) and low-γ neural oscillation (30-60 Hz) PAC in hippocampal CA3 area was analyzed by MATLAB wavelet packet extraction technique. The results showed that, compared with the general avoidance response group, the fast avoidance response group exhibited higher θ-γ neural oscillation PAC in hippocampal CA3 area before training. θ-γ oscillation PAC in hippocampal CA3 area was increased in both groups after training. It was also noticed that θ-γ neural oscillation PAC of some frequency bands in the general avoidance response group were significantly higher than those in the fast avoidance response group. The results suggest that certain intensity of training can change the spatial identifying and cognitive ability of rats, and the mechanism may involve the increase of the synchrony of θ-γ neural oscillation, i.e., the enhancement of θ-γ phase-amplitude alternating frequency coupling in hippocampal neurons.

Effect of θ­Î³ neural oscillation stimulation in hippocampal CA3 area on spatial cognition ability in rats

Objective: To investigate the effects of θ­Î³ neural oscillation stimulation in hippocampal CA3 area on spatial cognition ability in rats. Methods: According to the results of Y maze shock avoidance training, the rats were divided into fast avoidance response group and general avoidance response group. Using endogenous θ­Î³ neural oscillations from the fast avoidance response rats to perform deep brain stimulation in vivo to the left and right hippocampal CA3 region of rats with general avoidance response, then the spatial cognition was tested by Y maze shock avoidance training. The variation of θ oscillation and low-γ neural oscillation phase-amplitude coupling (PAC) in CA3 area was analyzed by wavelet packet extraction technique. Western blotting was used to detect the expression of N-methyl-D-aspartate receptor 2B subunit (NR2B) and postsynaptic density(PSD)-95 in hippocampal tissues of rats to explore its molecular mechanism. Results: Compared with the general avoidance response rats, the days to reach the standard, the training number, the correct response time and the error reaction number in simulated stimulus avoidance response rats were significantly reduced, but the correct response rate was significantly increased (all P<0.01); the θ­Î³ neural oscillations PAC in the hippocampal CA3 region in the simulated stimulus avoidance response rats (3­5 Hz and 30­34, 38­42, 44­48 Hz; 5­7 Hz and 42­46, 44­48, 54­58 Hz) were significantly higher than that in the general avoidance response rats (all P<0.05). Meanwhile, the protein expressions of NR2B and PSD-95 in hippocampal tissues were significantly increased (both P<0.05) in simulated stimulus avoidance response rats. Conclusion: The spatial cognition of normal avoidance response rats can be significantly improved by endogenous θ­Î³ neural oscillation stimulation to hippocampal CA3 region, which may be caused by the enhancement of synaptic plasticity mediated by NR2B and PSD-95.

Heroin exposure and withdrawal differentially influence expression of NMDA receptor NR2 subunits in the prelimbic region of rat medial prefrontal cortex.

It is widely reported that drug addiction involves the strengthening of specific reward circuits through N-methyl-d-aspartic acid receptor (NMDAR)-dependent synaptic potentiation, and several lines of evidence strongly implicate NMDA receptor 2 (NR2) subunits in drug abuse. To explore the potential mechanism of heroin dependence, this study examined changes in the expression levels of NR2 subunits NR2A-D in the prelimbic (PL) region of the medial prefrontal cortex (mPFC) after repeated heroin administration and subsequent abstinence. The conditioned place preference (CPP) test confirmed successful induction of heroin dependence and withdrawal. Western blotting and qRT-PCR revealed no differences in NR2A subunit expression among heroin-exposure, heroin-withdrawal, and control group rats; in contrast, expression of NR2B was significantly higher in the heroin-exposure group, whereas expression levels of NR2C and NR2D were significantly higher in the heroin-withdrawal group relative to the controls. Further studies are needed to identify the functional significance based on alterations of NR2 subunits.

Theta-gamma coupling in the prelimbic area is associated with heroin addiction.

The medial prefrontal cortex (mPFC) is implicated in the regulation of drug-seeking behavior, but the specific contributions of the mPFC prelimbic (PL) subdivision and the precise mechanisms underlying heroin abuse remain largely unclear. In the present study, we examined changes in the rhythmic ensemble activity of PL neurons after induction of heroin addiction in rats. Rats were injected daily with saline (control group) or heroin (addiction group) in the light chamber of a light-dark shuttle box, and a video tracking system was used to measure conditioned place preference (CPP) as a sign of addiction. A wireless telemetry system was used to record local field potentials (LFPs) from the PL area during expression of CPP. Before treatment, there was no difference in CPP between groups (P > 0.05). However, rats in the experimental group exhibited significant CPP (P < 0.05) in the light chamber after heroin treatment compared to before treatment and compared to control rats. During CPP, addicted rats demonstrated substantial alterations in relative θ and γ frequency band power (Ps < 0.05); moreover, the θ wave alteration was strongly coupled to γ waves in heat map analyses (P < 0.05). Collectively, these findings implicate heroin-induced alterations in PL area neural activity and θ-γ coupling in heroin addiction.

[EEG characteristics of medial prefrontal cortex in rats with morphine dependent place preference under shuttling condition].

OBJECTIVE: To study the correlation between EEG characteristics of medial prefrontal cortex (mPFC) and drug-seeking behavior of rats with morphine dependent place preference under shuttling condition. METHODS: Forty rats were randomly divided into four groups (n = 10): morphine PL group, NS PL group, morphine IL group and NS IL group. After embeding the electrode in prelimbic (PL) or infralimbic (IL) cortex of each group by brain stereotaxic operation, the model of morphine dependent conditioned place preference (CPP) in rats was established. The differences of EEG wave percentage in mPFC were telemetered and analyzed when rats shuttled before and after the model. RESULTS: After the model, the withdrawal symptoms were evident in morphine PL and IL group, and the activity time and distance in white box were increased obviously. Compared with control group, after the model, the EEG in morphine PL group showed that: when the rats shuttled to white box, 8 wave decreased obviously, P wave increased obviously. When the rats shuttled to black box, brain waves showed opposite changes. The EEG in morphine IL group showed that: when the rats shuttled to white box, a wave increased obviously, P and a wave decreased obviously. When the rats shuttled to black box, the brain wave had no significant differences compared with control group. CONCLUSION: The EEG changes are different in PL and IL cortex of morphine CPP rats under shuttling condition, and the EEG changes are also different when rats shuttling to white or black box. There is possibly different mechanism, when different drug-seeking environmental cues caused EEG changes in different regions of mPFC.

[The changes of electric shock avoidance response and local field potentials on hippocampal CA3 region of the adolescent rats with high fat feeding].

OBJECTIVE: To investigate the changes of shock avoidance response in Y maze and the real-time local field potentials (LFPs) on hippocampal CA3 region in adolescent rats with high fat feeding. METHODS: The juvenile rats of weaning 1 week were fed separately on basic feed (BF) and high fat diet (HFD) for 4 weeks until the puberty. Using the electric shock avoidance training method, the relevant parameters of reaching the learning standard of two groups of rats were recorded, and the LFPs of CA3 region in hippocampus were explored simultaneously by wireless telemetry. RESULTS: Compared with the BF group, the body weight of HFD rats were increased significantly(P<0.05), the rats percentage of reaching the learning standard within 1 to 2 days and the various parameters of shock avoidance recorded in training were all superior to those of BF group rat,the LFP rhythm of bilateral hippocampal CA3 region appeared to the desynchronizd fast wave. The θ and γ1 rhythms of right hippocampal CA3 region shown synchronous increase, but there was no coupling formation in phase-amplitude of the θ and γ1 rhythms. CONCLUSIONS: From juvenile to adolescent with HFD intake, the adolescent rat gained an increase significantly in weight,but the ability of shock avoidance and the function of hippocampus-dependent spatial cognition in Y maze had not be expected decline.

[Changes of theta oscillation of prelimbic cortex in heroin-induced CPP rats].

OBJECTIVE: To investigate the relationship between the changes of neural oscillations and the drug-seeking motivation,record the telemetric local field potentials (LFPs) of the prelimbic cortex (PrL) in the latency of drug-seeking behavior of conditioned place preference (CPP) rats induced by heroin. METHODS: The recording electrode was stereotactically implanted intothe PrL cortex of rats. The animals were then randomly divided into operation-only control and heroin-induced CPP groups, respectively. A CPP video system in combination with awireless telemetry device was used for recording LFPs when the rats shuttled between black-white chamber for drug-seeking. The LFPs were analyzed by fast Fourier transform (FFT) and wavelet packet extraction. RESULTS: Compared with operation-only control group, the LFPs recorded in PrL area of heroin-induced CPP group of rat during black-white chamber shuttling showed that the percentage of θ rhythm were increased in right and left PrL, the percentage of γ3 rhythm was increased in left PrL, the phase-amplitude coupling of θ and γ3 was increased in left PrL. After MK-801 Maleate micro injection to PrL area,drug-seeking behavior of rat was markedly reduced and the percentage of θ oscillation was depressed,the phase-amplitude coupling of θ and γ3 was depressed in left PrL compared with operation-only control group. CONCLUSIONS: These results suggest that increase of θ oscillations of PrL area may be related to the drug-seeking motivation and behavior launching in heroin-induced CPP groups of rat. The changes of θ oscillations also have close relationship with glutamatergic neuron and the receptor of it on PrL area.

[Alteration of neural oscillations in hippocampal CA3 area in the fast avoidance response rat before and after electric shock avoidance training].

The purpose of the present study is to explore the relationship of spatial learning ability and specific electrical activities of neural oscillations in the rat. The fast and general avoidance response groups were selected on the basis of the animals' responses to the electric shock in Y type maze, and their local field potentials (LFPs) of hippocampal CA3 area were recorded by wireless telemetry before and after shock avoidance training, respectively. The components of neural oscillations related to spatial identifying and learning ability were analyzed. The results showed that, compared with the general avoidance response group, the fast avoidance response group did not show any differences of LFPs in hippocampal CA3 area before electric shock avoidance trial, but showed significantly increased percentages of 0-10 Hz and 30-40 Hz rhythm in right hippocampal CA3 area after the shock avoidance training (P < 0.01 or P < 0.05). Fast Fourier transform showed that percentage increase of 0-10 Hz band occurred mainly in θ (3-7 Hz) frequency, and 30-40 Hz frequency change was equivalent to the γ1 band. Furthermore, compared with those before training, only the percentages of ß, ß2 (20-30 Hz) and γ1 rhythm increased (P < 0.01 or P < 0.05) in fast avoidance response rats after training, while the θ rhythm percentage remained unchanged. In contrast, θ rhythm percentage and the large amplitude (intensity: +2.5 - -2.5 db) θ waves in right CA3 area of general avoidance response rats were significantly reduced after training (P < 0.01). These results suggest that the increased percentages of ß2 and γ1 rhythm and high-level (unchanged) percentage of θ rhythm in the right hippocampus CA3 area might be related to strong spatial cognition ability of fast avoidance response rats.

[Analysis of Electroencephalogram Sample Entropy Measurement in Frontal Association Cortex Based on Heroin-induced Conditioned Place Preference in Rats].

To explore the relationship between the drug-seeking behavior, motivation of conditioned place preference (CPP) rats and the frontal association cortex (FrA) electroencephalogram (EEG) sample entropy, we in this paper present our studies on the FrA EEG sample entropy of control group rats and CPP group rats, respectively. We invested different behavior in four situations of the rat activities, i. e. rats were staying in black chamber of videoed boxes, those staying in white chamber of videoed boxes, those shuttling between black-white chambers and those shuttling between white-black chambers. The experimental results showed that, compared with the control group rats, the FrA EEG sample entropy of CPP rats staying in black chamber of video box and shuttling between white-black chambers had no significant difference. However, sample entropy is significantly smaller (P < 0.01) when heroin-induced group rats stayed in white chamber of video box and shuttled between black-white chambers. Consequently, the drug-seeking behavior and motivation of CPP rats correlated closely with the EEG sample entropy changes.

[Changes of telemetry electrical activity in the infralimbic cortex of morphine-dependent rats with extinguished drug-seeking behavior].

OBJECTIVE: To investigate the changes of telemetry electrical activity in the infralimbic cortex (IL) of morphine-dependent rats with extinguished drug-seeking behavior. METHODS: SD rats were randomly divided into model group and control group and received operations of brain stereotaxic electrode embedding in the IL. The rats in the model group were induced to acquire morphine dependence and then received subsequent extinction training, and the changes of electrical activity in the IL were recorded with a physical wireless telemetry system. RESULTS: In rats with morphine dependence, the time staying in the white box was significantly longer on days 1 and 2 after withdrawal than that before morphine injection and that of the control rats, but was obviously reduced on days 1 and 2 after extinction training to the control level. Compared with the control group, the morphine-dependent rats on day 2 following withdrawal showed significantly increased ß wave and decreased δ wave when they stayed in the white box but significantly increased δ wave and decreased α wave and ß wave when they shuttled from the black to the white box. On day 2 of extinction, the model rats, when staying in the white box, showed significantly decreased θ wave compared with that of the control rats group but decreased ß wave and θ wave and increased δ wave compared with those in the withdrawal period. When they shuttled from black to white box, the model rats showed decreased δ wave and increased α wave and ß wave compared with those in the withdrawal period. CONCLUSION: Morphine-dependent rats have abnormal changes of electrical activity in the IL in drug-seeking extinction to affect their drug-seeking motive and inhibit the expression and maintenance of drug-seeking behaviors.

[Telemetry electroencephalograph changes of temporal association cortex in heroin-induced conditioned place preference rats].

OBJECTIVE: To analyze the relationship between the electroencephalograph (EEG) changes of temporal association cortex (TeA) and the drug-seeking behavior in heroin-induced conditioned place preference (CPP) rats. METHODS: The rats were randomly divided into an operated control group and a heroin-induced CPP group after the electrodes were buried in TeA by stereotactic technology. The TeA EEG was recorded by the CPP video system combining with the EEG wireless telemetry, where the rats stayed in black or white chambers, shuttling from black to white chambers or from white to black chambers. RESULTS: Compared with the operated control group, the percentage of TeA θ waves was increased significantly when staying in black or white chambers in the heroin-induced CPP group (P<0.05, P<0.01). Compared with the operated control group, when rats shuttling between the 2 chambers, the TeA δ waves were reduced (P<0.01), but ß waves, ß2 waves in particular, were increased (P<0.01) in the heroin-induced CPP group (P<0.05, P<0.01). Compared with staying in the black chamber, when heroin-induced CPP rats were shuttling between black and white chambers, the right TeA θ waves were reduced, and ß waves, ß2 waves in particular, were increased (P<0.01). Compared staying in the white chamber with shuttling between white and black chambers in the heroin induced CPP rats, the right TeA θ waves, but not ß waves, were reduced (P<0.01). CONCLUSION: The EGG changes on the right TeA in the heroin-induced CPP rats, including the increased fast waves (ß, ß2) and the reduced slow wave (θ), may be related to drug-seeking behaviors.

[A wireless telemetry study on the electrical activity in nucleus accumbens of heroin-induced place preference rats].

OBJECTIVE: To analyze the electrical activity property changes in nucleus accumbens (NAc) of heroin-induced conditioned place preference (CPP) rats during different stages of heroin dependence and to explore NAc's roles in the formation of drug dependence. METHODS: Recording electrodes were bilaterally embedded into the NAcs of rats with the aid of stereotaxic apparatus, followed by establishment of heroin-dependent rat model. The NAc electrical activity during 3 different stages of heroin dependence, including heroin pre-exposure, immediate post-exposure and heroin withdrawal, were respectively recorded using EEG wireless telemetry techniques. The frequency distribution (ranging from 0.5 to 30 Hz) and the amplitude of NAc electrical activity were analyzed and measured. RESULTS: Heroin-dependent rat models were successfully established and their withdrawal symptoms were evident. All rats showed a conditioned place preference (CPP) for the white box after 5-10 days of heroin-exposure, and displayed a maximum withdrawal symptoms on 2d after heroin- withdrawal. During all statges of heroin-dependence, the NAc electrical activity contained the highest proportion of delta rhythm and the lowest proportion of alpha2 rhythm. The discharge frequence band was similar across different stages. There was a significantly increased ratio of low-frequency discharges (delta rhythm) and decreased ratio of high-frequency discharges (beta rhythm) in NAc of rats during the immediate post- heroin exposure stage when compared with that during pre-exposure and heroin withdrawal stages. During the withdrawal stage, the ratio of at rhythm was significantly lower than during pre- and post-heroin exposure stages (P < 0.01). Further, the mean discharge amplitude in NAcs during immediate post-exposure and withdrawal stages was significantly increased relative to pre-exposure stage. However, the mean discharge amplitude during heroin withdrawal stage was significantly lower than during immediate post-exposure stage. CONCLUSION: The electrical activity properties in rat NAcs showed a significant change during different stages of heroin-dependence, which suggested that neuronal activities in NAcs might contribute to the modulation of drug-dependence.

[Telemetry EEG of parietal association cortex in heroin-induced CPP rats].

OBJECTIVE: To determine the relationship between EEG changes of parietal association cortex (PtA) and drug-seeking behaviors of heroin-induced conditioned place preference (CPP) rats. METHODS: Stereotaxic electrode was buried in the PtA of rats, which were then divided randomly into heroin-induced CPP group and operation-only control group. A CPP video system in combination with EEG wireless telemetry was used for recording PtA EEG and the behaviors of the rats-staying in black or white chamber of the video box; shuttling between black-white chambers or between white-black chambers. RESULTS: No significant difference in percentage of the telemetry EEG waves was found between the two groups of rats when they stayed in the black or white chambers. The heroin-induced CPP rats had increased percentage of delta waves (P < 0.05) on the right PtA and decreased percentage of beta and beta2 waves on both right and left PtA (P < 0.05) when they shuttled between two chambers. Compared with the operation-only controls, significant decrease in the percentage of delta waves on both left and right PtA and increase in theta, alpha and alpha1 waves were evident (P < 0.05) only when the heroin-induced CPP rats shuttled between white-black chambers. CONCLUSION: EEG changes on PtA of heroin-induced CPP rats differ between staying and shuttling states. Such changes may not be associated with drug-seeking behaviors.

Age-related changes of structures in cerebellar cortex of cat.

We studied the structures of the cerebellar cortex of young adult and old cats for age-related changes, which were statistically analysed. Nissl staining was used to visualize the cortical neurons. The immunohistochemical method was used to display glial fibrillary acidic protein (GFAP)-immunoreactive (IR) astrocytes and neurofilament-immunoreactive (NF-IR) neurons. Under the microscope, the thickness of the cerebellar cortex was measured; and the density of neurons in all the layers as well as that of GFAP-IR cells in the granular layer was analysed. Compared with young adult cats, the thickness of the molecular layer and total cerebellar cortex was significantly decreased in old cats, and that of the granular layer increased. The density of neurons in each layer was significantly lower in old cats than in young adult ones. Astrocytes in old cats were significantly denser than in young adult ones, and accom-panied by evident hypertrophy of the cell bodies and enhanced immunoreaction of GFAP substance. Purkinje cells (PCs) in old cats showed much fewer NF-IR dendrites than those in young adults. The above findings indicate a loss of neurons and decrease in the number of dendrites of the PCs in the aged cerebellar cortex, which might underlie the functional decline of afferent efficacy and information integration in the senescent cerebellum. An age-dependent enhancement of activity of the astrocytes may exert a protective effect on neurons in the aged cerebellum.