Stimulus-specific adaptation (SSA), defined as a decrease in responses to a common stimulus that only partially generalizes to other rare stimuli, is a widespread phenomenon in the brain that is believed to be related to novelty detection. Although cross-modal sensory processing is also a widespread phenomenon, the interaction between the two phenomena is not well understood. In this study, the thalamic reticular nucleus (TRN), which is regarded as a hub of the attentional system that contains multi-modal neurons, was investigated. The results showed that SSA existed in an interactive oddball stimulation, which mimics stimulation changes from one modality to another. In the bimodal integration, SSA to bimodal stimulation was stronger than to visual stimulation alone but similar to auditory stimulation alone, which indicated a limited integrative effect. Collectively, the present results provide evidence for independent cross-modal processing in bimodal TRN neurons.
Acoustic Stimulation ; Animals ; Auditory Perception/physiology* ; Geniculate Bodies ; Rats ; Rats, Wistar ; Thalamic Nuclei/physiology*

The thalamostriatal pathway is implicated in Parkinson's disease (PD); however, PD-related changes in the relationship between oscillatory activity in the centromedian-parafascicular complex (CM/Pf, or the Pf in rodents) and the dorsal striatum (DS) remain unclear. Therefore, we simultaneously recorded local field potentials (LFPs) in both the Pf and DS of hemiparkinsonian and control rats during epochs of rest or treadmill walking. The dopamine-lesioned rats showed increased LFP power in the beta band (12 Hz-35 Hz) in the Pf and DS during both epochs, but decreased LFP power in the delta (0.5 Hz-3 Hz) band in the Pf during rest epochs and in the DS during both epochs, compared to control rats. In addition, exaggerated low gamma (35 Hz-70 Hz) oscillations after dopamine loss were restricted to the Pf regardless of the behavioral state. Furthermore, enhanced synchronization of LFP oscillations was found between the Pf and DS after the dopamine lesion. Significant increases occurred in the mean coherence in both theta (3 Hz-7 Hz) and beta bands, and a significant increase was also noted in the phase coherence in the beta band between the Pf and DS during rest epochs. During the treadmill walking epochs, significant increases were found in both the alpha (7 Hz-12 Hz) and beta bands for two coherence measures. Collectively, dramatic changes in the relative LFP power and coherence in the thalamostriatal pathway may underlie the dysfunction of the basal ganglia-thalamocortical network circuits in PD, contributing to some of the motor and non-motor symptoms of the disease.
Animals ; Brain Waves ; physiology ; Corpus Striatum ; physiopathology ; Cortical Synchronization ; physiology ; Dopaminergic Neurons ; physiology ; Electrocorticography ; Male ; Neural Pathways ; physiopathology ; Oxidopamine ; Parkinsonian Disorders ; physiopathology ; Rats, Wistar ; Thalamic Nuclei ; physiopathology ; Walking ; physiology

BACKGROUNDThe antiepileptic effect of the anterior thalamic nuclei (ANT) stimulation has been demonstrated; however, its underlying mechanism remains unclear. The aim of this study was to investigate the effect of chronic ANT stimulation on hippocampal neuron loss and apoptosis.

METHODSSixty-four rats were divided into four groups: The control group, the kainic acid (KA) group, the sham-deep brain stimulation (DBS) group, and the DBS group. KA was used to induce epilepsy. Seizure count and latency to the first spontaneous seizures were calculated. Nissl staining was used to analyze hippocampal neuronal loss. Polymerase chain reaction and Western blotting were conducted to assess the expression of caspase-3 (Casp3), B-cell lymphoma-2 (Bcl2), and Bcl2-associated X protein (Bax) in the hippocampal CA3 region. One-way analysis of variance was used to determine the differences between the four groups.

RESULTSThe latency to the first spontaneous seizures in the DBS group was significantly longer than that in the KA group (27.50 ± 8.05 vs. 16.38 ± 7.25 days, P = 0.0005). The total seizure number in the DBS group was also significantly reduced (DBS vs. KA group: 11.75 ± 6.80 vs. 23.25 ± 7.72, P = 0.0002). Chronic ANT-DBS reduced neuronal loss in the hippocampal CA3 region (DBS vs. KA group: 23.58 ± 6.34 vs. 13.13 ± 4.00, P = 0.0012). After chronic DBS, the relative mRNA expression level of Casp3 was decreased (DBS vs. KA group: 1.18 ± 0.37 vs. 2.09 ± 0.46, P = 0.0003), and the relative mRNA expression level of Bcl2 was increased (DBS vs. KA group: 0.92 ± 0.21 vs. 0.48 ± 0.16, P = 0.0004). The protein expression levels of CASP3 (DBS vs. KA group: 1.25 ± 0.26 vs. 2.49 ± 0.38, P < 0.0001) and BAX (DBS vs. KA group: 1.57 ± 0.49 vs. 2.80 ± 0.63, P = 0.0012) both declined in the DBS group whereas the protein expression level of BCL2 (DBS vs. KA group: 0.78 ± 0.32 vs. 0.36 ± 0.17, P = 0.0086) increased in the DBS group.

CONCLUSIONSThis study demonstrated that chronic ANT stimulation could exert a neuroprotective effect on hippocampal neurons. This neuroprotective effect is likely to be mediated by the inhibition of apoptosis in the epileptic hippocampus.

Animals ; Anterior Thalamic Nuclei ; physiology ; Apoptosis ; Deep Brain Stimulation ; Epilepsy ; pathology ; therapy ; Hippocampus ; pathology ; Kainic Acid ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Seizures ; prevention & control

BACKGROUNDRecent clinical and preclinical studies have suggested that deep brain stimulation (DBS) can be used as a tool to enhance cognitive functions. The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit, including the anterior nucleus of thalamus (ANT), the entorhinal cortex (EC), and the fornix (FX), on cognitive behaviors in an Alzheimer's disease (AD) rat model.

METHODSForty-eight rats were subjected to an intrahippocampal injection of amyloid peptides 1-42 to induce an AD model. Rats were divided into six groups: DBS and sham DBS groups of ANT, EC, and FX. Spatial learning and memory were assessed by the Morris water maze (MWM). Recognition memory was investigated by the novel object recognition memory test (NORM). Locomotor and anxiety-related behaviors were detected by the open field test (OF). By using two-way analysis of variance (ANOVA), behavior differences between the six groups were analyzed.

RESULTSIn the MWM, the ANT, EC, and FX DBS groups performed differently in terms of the time spent in the platform zone (F(2,23) = 6.04, P < 0.01), the frequency of platform crossing (F(2,23) = 11.53, P < 0.001), and the percent time spent within the platform quadrant (F(2,23) = 6.29, P < 0.01). In the NORM, the EC and FX DBS groups spent more time with the novel object, although the ANT DBS group did not (F(2,23) = 10.03, P < 0.001). In the OF, all of the groups showed a similar total distance moved (F (1,42) = 1.14, P = 0.29) and relative time spent in the center (F(2,42) = 0.56, P = 0.58).

CONCLUSIONSOur results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently than ANT DBS. In addition, hippocampus-independent recognition memory was enhanced by EC and FX DBS. None of the targets showed side-effects of anxiety or locomotor behaviors.

Alzheimer Disease ; physiopathology ; therapy ; Animals ; Anterior Thalamic Nuclei ; physiology ; Deep Brain Stimulation ; methods ; Entorhinal Cortex ; physiology ; Fornix, Brain ; physiology ; Male ; Memory ; physiology ; Rats ; Rats, Sprague-Dawley ; Spatial Learning ; physiology

BACKGROUNDElectrical stimulation of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures. In this study, we investigated changes in glucose metabolism during high-frequency stimulation of ANT in epileptic rats.

METHODSThree groups of rats were used: (1) a stimulation group (n = 12), (2) a sham stimulation group (n = 12) with seizures induced by stereotactic administration of kainic acid (KA), and (3) a control group (n = 12) with sham surgery. Concentric bipolar electrodes were stereotaxically implanted unilaterally in the ANT. High-frequency stimulation was performed in each group except the sham stimulation group. Microdialysis probes were lowered into the CA3 region of the hippocampus unilaterally but bilaterally in the stimulation group. The concentrations of glucose, lactate, and pyruvate in dialysate samples were determined by an ISCUS microdialysis analyzer.

RESULTSThe extracellular concentrations of lactate and lactate/pyruvate ratio (LPR) of epileptic rats were significantly higher than in control rats (P = 0.020, P = 0.001; respectively). However, no significant difference in the concentration of glucose and pyruvate was found between these groups (P > 0.05). Electrical stimulation of ANT induced decreases in lactate and LPR in the ipsilateral hippocampus (KA injected) of the stimulation group (P < 0.05), but it did not influence the glucose metabolism in the contralateral hippocampus (P > 0.05).

CONCLUSIONSThis study demonstrated that the glycolysis was inhibited in the ipsilateral hippocampus of epileptic rats during electrical ANT stimulation. These findings may provide useful information for better understanding the mechanism of ANT-deep brain stimulation.

Animals ; Anterior Thalamic Nuclei ; physiology ; Deep Brain Stimulation ; Epilepsy ; metabolism ; therapy ; Glucose ; metabolism ; Glycolysis ; Hippocampus ; metabolism ; Male ; Rats ; Rats, Wistar

Parkinson's disease is a progressive neurodegenerative disorder characterized clinically by rigidity, akinesia, resting tremor and postural instability. It has recently been suggested that low frequency stimulation of the pedunculopontine nucleus (PPN) has a role in the therapy for Parkinsonism, particularly in gait disorder and postural instability. However, there is limited information about the mechanism of low frequency stimulation of the PPN on Parkinson's disease. The present study was to investigate the effect and mechanism of low frequency stimulation of the PPN on the firing rate of the ventrolateral thalamic nucleus (VL) in a rat model with unilateral 6-hydroxydopamine lesioning of the substantia nigra pars compacta. In vivo extracellular recording and microiontophoresis were adopted. The results showed that the firing rate of 60.71% VL neurons in normal rats and 59.57% VL neurons in 6-hydroxydopamine lesioned rats increased with low frequency stimulation of the PPN. Using microiontophoresis to VL neurons, we found the firing rate in VL neurons responded with either an increase or decrease in application of acetylcholine (ACh) in normal rats, whereas with a predominant decrease in M receptor antagonist atropine. Furthermore, the VL neurons were mainly inhibited by application of γ-aminobutyric acid (GABA) and excited by GABA(A) receptor antagonist bicuculline. Importantly, the VL neurons responding to ACh were also inhibited by application of GABA. We also found that the excitatory response of the VL neurons to the low frequency stimulation of the PPN was significantly reversed by microiontophoresis of atropine. These results demonstrate that cholinergic and GABAergic afferent nerve fibers may converge on the same VL neurons and they are involved in the effects of low frequency stimulation of the PPN, with ACh combining M(2) receptors on the presynaptic membrane of GABAergic afferents, which will inhibit the release of GABA in the VL and then improve the symptoms of Parkinson's disease.
Acetylcholine ; metabolism ; Action Potentials ; Animals ; Cholinergic Fibers ; physiology ; Electric Stimulation ; Male ; Oxidopamine ; Parkinson Disease, Secondary ; chemically induced ; physiopathology ; therapy ; Pedunculopontine Tegmental Nucleus ; physiology ; Rats ; Rats, Sprague-Dawley ; Ventral Thalamic Nuclei ; physiology

BACKGROUNDAlthough thalamotomy could dramatically improve both parkinsonian resting tremor and essential tremor (ET), the mechanisms are obviously different. This study aimed to investigate the neuronal activities in the ventrolateral thalamus of Parkinson's disease (PD) and ET.

METHODSThirty-six patients (PD: 20, ET: 16) were studied. Microelectrode recordings in the ventral oral posterior (Vop) and the ventral intermediate nucleus (Vim) of thalamus was performed on these patients who underwent thalamotomy. Electromyography (EMG) was recorded simultaneously on the contralateral limbs to surgery. Single unit analysis and the interspike intervals (ISIs) were measured for each neuronal type. ISI histogram and auto-correlograms were constructed to estimate the pattern of neuronal firing. Mann-Whitney test and Kruskal-Wallis (K-W) test were used to compare the mean spontaneous firing rate (MSFR) of neurons of PD and ET patients.

RESULTSThree hundred and twenty-three neurons were obtained from 20 PD trajectories, including 151 (46.7%) tremor related neuronal activity, 74 neurons (22.9%) with tonic firing, and 98 (30.4%) neurons with irregular discharge. One hundred and eighty-seven neurons were identified from 16 ET trajectories including 46 (24.6%) tremor-related neuronal activity, 77 (41.2%) neurons with tonic firing, and 64 neurons (34.2%) with irregular discharge. The analysis of MSFR of neurons with tonic firing was 26.7 (3.4 - 68.3) Hz (n = 74) and that of neurons with irregular discharge (n = 98) was 13.9 (3.0 - 58.1) Hz in PD; whereas MSFR of neurons with tonic firing (n = 77) was 48.8 (19.0 - 135.5) Hz and that of neurons with irregular discharge (n = 64) was 26.3 (8.7 - 84.7) Hz in ET. There were significant differences in the MSFR of two types of neuron for PD and ET (K-W test, both P < 0.05). Significant differences in the MSFR of neuron were also obtained from Vop and Vim of PD and ET (16.3 Hz vs. 34.8 Hz, 28.0 Hz vs. 49.9 Hz) (K-W test, both P < 0.05), respectively.

CONCLUSIONIn consistent with recent findings, the decreased MSFR of neurons observed in the Vop is likely to be involved in PD whereas the increased MSFR of neurons seen in the Vim may be a cause of ET.

Essential Tremor ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Neurons ; physiology ; Parkinson Disease ; physiopathology ; Retrospective Studies ; Ventral Thalamic Nuclei ; physiopathology

The purpose of this study was to investigate the influence of electrical stimulation of anterior cingulate cortex (ACC) on spontaneous activity of neurons in thalamic ventrobasal nucleus (VB). Experiments were performed on 12 male Sprague-Dawley rats weighing 250-310 g (4-5 months old). According to Paxinos and Watson's coordinate atlas of the rat, the frontal and parietal cortical areas were exposed by craniotomy, the recording electrodes were then inserted into the VB (P 2.4-4.1 mm, R 2.0-3.5 mm, H 5.2-6.8 mm) and the stimulating electrodes into the ACC (A 1.1-3.0 mm, R 0.0-1.0 mm, H 1.5-2.4 mm). Single-unit activities were recorded extracellularly in the VB by glass micropipettes (impedance 3-8 MOmega) filled with 0.5 mol/L sodium acetate solution containing saturated Fast Green. To study the effects of ACC activation on the spontaneous activities of VB cells, single electrical pulse (0.2 ms duration) was delivered to the ACC by a concentric bipolar stainless steel electrode (0.32 mm outer diameter). An effective ACC stimulation was determined for each VB neuron by gradually increasing the current intensity from 0.1 mA until either a significant change in the spontaneous activity of the VB neuron was observed, or the current intensity reached 0.4 mA. The results showed that ACC stimulation significantly suppressed the spontaneous activities in 12 out of 53 VB neurons (22.6%). (1) After the stimulation was delivered to ACC, the spontaneous activities of different VB neurons were totally suppressed for different time span. (2) There was obvious dose-effect relevance between ACC stimulation intensity and their inhibitory effect. The duration of complete inhibition was prolonged with the increases in the intensity and number of stimulation impulses in ACC. (3) The stimulation in the ACC depressed the spontaneous activities of VB neurons in different forms and this inhibition exhibited an accumulative effect. All these results indicate that the stimulation of ACC exerts an inhibitory influence on the spontaneous activities of VB neurons.
Animals ; Electric Stimulation ; Gyrus Cinguli ; physiology ; Male ; Neurons ; cytology ; Rats ; Rats, Sprague-Dawley ; Thalamic Nuclei ; cytology

BACKGROUNDIt has been proposed that parkinsonian motor signs result from hyperactivity in the output nucleus of the basal ganglia, which suppress the motor thalamus and cortical areas. This study aimed to explore the neuronal activity in the globus pallidus internus (GPi) and the ventrolateral thalamic nuclear group (ventral oral posterior/ventral intermediate, Vop/Vim) in patients with Parkinson's disease (PD).

METHODSTwenty patients with PD who underwent neurosurgery were studied. Microelectrode recording was performed in the GPi (n = 10) and the Vop/Vim (n = 10) intraoperatively. Electromyography (EMG) contralateral to the surgery was simultaneously performed. Single unit analysis was carried out. The interspike intervals (ISI) and coefficient of variation (CV) of ISI were calculated. Histograms of ISI were constructed. A unified Parkinson's disease rating scale (UPDRS) was used to assess the clinical outcome of surgery.

RESULTSThree hundred and sixty-three neurons were obtained from 20 trajectories. Of 175 GPi neurons, there were 15.4% with tremor frequency, 69.2% with tonic firing, and 15.4% with irregular discharge. Of 188 thalamic neurons, there were 46.8% with tremor frequency, 22.9% with tonic firing, and 30.3% with irregular discharge. The numbers of three patterns of neuron in GPi and Vop/Vim were significantly different (P < 0.001). ISI analysis revealed that mean firing rate of the three patterns of GPi neurons was (80.9 +/- 63.9) Hz (n = 78), which was higher than similar neurons with 62.9 Hz in a normal primate. For the Vop/Vim group, ISI revealed that mean firing rate of the three patterns of neurons (n = 95) was (23.2 +/- 17.1) Hz which was lower than similar neurons with 30 Hz in the motor thalamus of normal primates. UPDRS indicated that the clinical outcome of pallidotomy was (64.3 +/- 29.5)%, (83.4 +/- 19.1)% and (63.4 +/- 36.3)%, and clinical outcome of thalamotomy was (92.2 +/- 12.9)%, (68.0 +/- 25.2)% and (44.3 +/- 27.2)% for tremor, rigidity and bradykinesia, respectively. A significant difference of tremor and rigidity was found between GPi and Vop/Vim (P < 0.05).

CONCLUSIONSDifferent changes in neuronal firing rate and the pattern in GPi and Vop/Vim are likely responsible for parkinsonian motor signs. The results support the view that abnormal neuronal activity in GPi and Vop/Vim are involved in the pathophysiology of parkinsonism.

Adult ; Aged ; Female ; Globus Pallidus ; physiopathology ; Humans ; Male ; Middle Aged ; Neurons ; physiology ; Parkinson Disease ; physiopathology ; Ventral Thalamic Nuclei ; physiopathology

AIMTo investigate the changes in neuronal activities of the pedunculopontine nucleus (PPN) and the ventrolateral thalamic nucleus (VL) after unilateral 6-hydroxydopamin (6-OHDA) lesioning of the striatum in rats.

METHODSExtracellular single-unit recordings were perin normal rats and 6-OHDA lesioned rats to observe the firing rate and firing pattern occurring in PPN and VL neurons.

RESULTSThe firing rate of PPN neurones significantly increased from (8.31 +/- 0.62) Hz in normal rats to (10.70 +/- 0.85) Hz in 6-OHDA lesioned rats. The firing pattern changed towards more irregular and bursty when compared with the normal rats, with the firing rate increasing in regular pattern. The firing rate of VL neurones in normal rats and 6-OHDA lesioned rats were (6.25 +/- 0.54) Hz and (5.67 +/- 0.46)Hz respectively, whereas to normal animals. Surthere were no significant differences in these two groups. In addition, the firing pattern did not change in VL compared prisingly, the firing rate in burst pattern decreased significantly.

CONCLUSIONThese findings demonstrate that PPN neurons are overactive in 6-OHDAlesioned rats, indicating the participation of this nucleus in the pathophysiology of parkinsonism and the activities of VL neurons might be regulated by projection from PPN to VL.

Action Potentials ; physiology ; Animals ; Corpus Striatum ; physiopathology ; Male ; Neural Pathways ; injuries ; pathology ; physiopathology ; Neurons ; physiology ; Oxidopamine ; toxicity ; Parkinson Disease ; pathology ; physiopathology ; Pedunculopontine Tegmental Nucleus ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; injuries ; pathology ; physiopathology ; Ventral Thalamic Nuclei ; physiopathology