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Donald J Woodward

Publications and source records attributed to Donald J Woodward.

17 recordsLinked to original sources
PubMed2006

Inhibitory gating of single unit activity in amygdala: effects of ketamine, haloperidol, or nicotine.

BACKGROUND: Inhibitory gating is thought to be a basic process for filtering incoming stimuli to the brain. Little information is currently available concerning local neural networks of inhibitory gating or the intrinsic neurochemical substrates involved in the process. METHODS: The goal of the present study was to examine the pharmacological aspects of inhibitory gating from single units in the amygdala. We tested the effects of ketamine (80 mg/kg) and haloperidol (1 mg/kg) on inhibitory gating. Additionally, we examined the effect of nicotine (1.2 mg/kg) on single unit gating in this same brain structure. RESULTS: We found that in one subset of neurons, ketamine administration significantly reduced tone responsiveness with a subsequent loss of inhibitory gating, whereas the other subset persisted in both auditory responding and gating albeit at a weaker level. Haloperidol and nicotine had very similar effects, exemplified by a dramatic increase in the response to the initial "conditioning" tone with a subsequent improvement in inhibitory gating. CONCLUSIONS: Tone responsiveness and inhibitory gating persists in a subset of neurons after glutamate N-methyl-D-aspartate receptor blockade. Dopamine and nicotine modulate gating in these normal animals and have similar effects of enhancing responsiveness to auditory stimulation at the single unit and evoked potential level.

Acoustic Stimulation↗
PubMed2006

Temporal sequence of ictal discharges propagation in the corticolimbic basal ganglia system during amygdala kindled seizures in freely moving rats.

We used a multiple channel, single unit recording technique to investigate the neural activity in different corticolimbic and basal ganglia regions in freely moving rats before and during generalized amygdala kindled seizures. Neural activity was recorded simultaneously in the sensorimotor cortex (Ctx), hippocampus, amygdala, substantia nigra pars reticulata (SNr) and the subthalamic nucleus (STN). We observed massive synchronized activity among neurons of different brain regions during seizure episodes. Neurons in the kindled amygdala led other regions in synchronized firing, revealed by time lags of neurons in other regions in crosscorrelogram analysis. While there was no obvious time lag between Ctx and SNr, the STN and hippocampus did lag behind the Ctx and SNr in correlated firing. Activity in the amygdala and SNr contralateral to the kindling stimulation site lagged behind their ipsilateral counterparts. However, no time lag was found between the kindling and contralateral sides of Ctx, hippocampus and STN. Our data confirm that the amygdala is an epileptic focus that emits ictal discharges to other brain regions. The observed temporal pattern indicates that ictal discharges from the amygdala arrive first at Ctx and SNr, and then spread to the hippocampus and STN. The simultaneous activation of both sides of the Ctx suggests that the neocortex participates in kindled seizures as a unisonant entity to provoke the clonic motor seizures. Early activation of the SNr (before the STN and hippocampus) points to an important role of the SNr in amygdala kindled seizures and supports the view that different SNr manipulations may be effective ways to control seizures.

Amygdala↗
PubMed2006

Basal ganglia neural responses during behaviorally effective deep brain stimulation of the subthalamic nucleus in rats performing a treadmill locomotion test.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). In spite of proven therapeutic success, the mechanism underlying the benefits of DBS has not been resolved. A multiple-channel single-unit recording technique was used in the present study to investigate basal ganglia (BG) neural responses during behaviorally effective DBS of the STN in a rat model of PD. Rats underwent unilateral dopamine (DA) depletion by injection of 6-hydroxyDA (6-OHDA) into one side of the medial forebrain bundle and subsequently developed a partial akinesia, which was assessed during the treadmill locomotion task. High frequency stimulation (HFS) of the STN restored normal treadmill locomotion behavior. Simultaneous recording of single unit activity in the striatum (STR), globus pallidus (GP), substantia nigra pars reticulata (SNr), and STN revealed a variety of neural responses during behaviorally effective HFS of the STN. Predominant inhibitory responses appeared in the STN stimulation site. Nearly equal numbers of excitatory and inhibitory responses were found in the GP and SNr, whereas more rebound excitatory responses were found in the STR. Mean firing rate did not change significantly in the STR, GP, and SNr, but significantly decreased in both sides of STN during DBS. A decrease in firing rate in the contralateral side of STN provides neural substrate for the clinical observation that unilateral DBS produces bilateral benefits in patients with PD. In addition to the firing rate changes, a decrease in burst firing was observed in the GP and STN. The present study indicates that DBS induces complex modulations of the BG circuit and further suggests that BG network reorganization, rather than a simple excitation or inhibition, may underlie the therapeutic effects of DBS in patients with PD.

Adrenergic Agents↗
PubMed2006

Dynamic neuronal responses in cortical and thalamic areas during different phases of formalin test in rats.

Although formalin-induced activity in primary afferent fibers and spinal dorsal horn is well described, the forebrain neural basis underlying each phase of behavior in formalin test has not yet been clarified. The present study was designed to investigate the cortical and thalamic neuronal responses and interactions among forebrain areas during different phases after subcutaneous injection of formalin. Formalin-induced neuronal activities were simultaneously recorded from primary somatosensory cortex (SI), anterior cingulate cortex (ACC) and medial dorsal (MD) and ventral posterior (VP) thalamus during different phases (i.e., first phase, interphase, second phase and third recovery phase starting from 70 min after injection) of formalin test, using a multi-channel, single-unit recording technique. Our results showed that, (i) unlike the responses in primary afferent fibers and spinal dorsal horn, many forebrain neurons displayed monophasic excitatory responses in the first hour after formalin injection, except a small portion of neurons which exhibited biphasic responses; (ii) the response patterns of many cortical and thalamic neurons changed from excitatory to inhibitory at the end of the second phase; (iii) the direction of information flow also changed dramatically, i.e., from cortex to thalamus and from the medial to the lateral pathway in the first hour, but reversed in phase 3. These results indicate that the changes of activity pattern in forebrain networks may underlie the emerging and subsiding of central sensitization-induced pain behavior in the second phase of formalin test.

Action Potentials↗
PubMed2005

Neural responses in multiple basal ganglia regions following unilateral dopamine depletion in behaving rats performing a treadmill locomotion task.

To investigate basal ganglia (BG) neural responses to dopamine (DA) depletion, multiple channel, single unit recording was carried out in freely moving rats performing a treadmill locomotion task. Single unit activity from 64 microelectrodes in the striatum (STR), globus pallidus (GP), subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) was recorded simultaneously before and after a unilateral DA lesion induced by microinjection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. The DA lesion resulted in an impairment of treadmill walking manifested by a significant decrease in swing time of both forelimbs. The stance time, however, increased significantly only in ipsilateral (good) forelimbs, reflecting compensatory changes in the good limb for motor deficits. Neural activity in the STR and GP ipsilateral to the lesion decreased during the 7-day period following the DA lesion. Conversely, an increase in spike discharges appeared in the ipsilateral SNr and STN several days after the DA lesion. Changes in the type of neural response associated with treadmill locomotion were also found in some neurons after DA depletion. Such changes were most prominent in the STR. Limb movement-related neural activity increased significantly mainly in the SNr. Additionally, neural responses to the tone cue associated with the onset of the treadmill diminished greatly in the lesioned side of the BG. Increased activity in SNr neurons is consistent with the concept that inhibition of thalamus contributes to hypokinesis in the absence of DA. Substantial decrease in striatal activity supports a concept that DA loss leads to a global suppression of recurrent cortical striatal thalamic activity that degrades normal information flow in Parkinson's diseases.

Action Potentials↗
PubMed2005

Coding of peripheral electrical stimulation frequency in thalamocortical pathways.

Frequency information of the environment is an important feature for sensory perception. It has been demonstrated that cortical and thalamic neurons exhibited frequency-specific responses to peripheral stimulation. In the present study, we investigated the effects of 1-100 Hz peripheral electrical stimulations on various thalamic and cortical areas in awake rats. We used chronically implanted microelectrode arrays to record neural activities from the anterior cingulate cortex, primary somatosensory cortex, and medial dorsal and ventral posterior thalamus. The results revealed that cortical and thalamic neurons exhibited frequency-specific responses at both single-neuron and ensemble levels. Clusters of neurons responded to different frequency ranges with changes of both the peak firing rates and the phases of the peak responses in a stimulation cycle. Partial directed coherence analysis showed that information flowing between these recorded areas is also enhanced or inhibited in some frequency-specific pattern during stimulation. These evidences suggest that central nervous system may code environmental frequency information mainly with the activation of selected neural circuits according to their own intrinsic electrical properties. These properties, in turn, may facilitate or inhibit their responses when stimulation with specific frequency information arrives.

Animals↗
PubMed2005

Auditory inhibitory gating in the amygdala: single-unit analysis in the behaving rat.

Inhibitory sensory gating has been proposed to be a fundamental physiological process that filters neural input. Its temporal properties could allow for a rapid influence on vigilance and attention processes. Inhibitory mechanisms are reflected by reductions in neural responsiveness to repeated and well-predicted stimuli; for auditory gating, this translates into an inhibition of the neural activation to subsequent tone stimuli embedded within sequential and identical tone presentations. Here we expand previous neurophysiological data on inhibitory gating by examining gating in the amygdala using single-unit recording in freely moving animals. Previous data have shown the amygdala to be important in mediating rapid auditory sensory processing involved in emotional conditioning. We measured inhibitory gating with two matching auditory tones presented in a repetitive fashion (10 ms tones, ISI = 500 ms and 10 s between pairs) for 1 h (360 pairs). The majority of the tone responsive units showed inhibitory gating (78/95 units) located in both the medial and lateral subnuclei of the amygdala. Different types of tone responses were gated, including both shorter- and longer-duration excitatory tone responses as well as inhibitory tone responses. Different degrees of gating were found ranging from 100% inhibition (complete gating category) to 25% inhibition (graded gating category). The degree of gating varied over short-term and long-term time intervals. These findings demonstrate the existence of inhibitory gating in the amygdala and provide a detailed description of the basic properties of this rapid neural inhibition that could play an important role in filtering stimulus input.

Acoustic Stimulation↗
PubMed2005

Restraint increases dopaminergic burst firing in awake rats.

In anesthetized animals, dopamine neurons fire in tonic and phasic firing modes hypothesized to be regulated by dissociable circuit mechanisms. Salient events critical to learning, reward processing, and attentional selection elicit transient phasic bursts. It is unclear, however, how burst activity contributes to sustained firing patterns in awake animals and if behavioral conditions known to affect dopaminergic neurotransmission change impulse activity levels. Acute stress is known to increase extracellular dopamine in the striatum and the prefrontal cortex. In this study, we have used multiunit recording to define and follow activity patterns in single dopaminergic neurons across days and to determine how restraint, a model of acute stress, changes tonic and phasic firing patterns. Long-term recording shows that a population of 23 putative dopamine neurons has heterogeneous firing profiles under baseline conditions. In all, 62% showed significant burst activity under resting conditions, while others showed predominantly regular (17%) or random (21%) activity patterns. Restraint increased mean firing rate in all dopamine neurons, but preferentially increased burst firing in neurons with higher burst rates under resting conditions. Finally, we show that increased burst firing can persist 24 h after a single exposure to stress. These data indicate that subsets of dopamine neurons may be sensitive to circuit mechanisms activated by stress and that persistent changes in burst firing may be evidence of synaptic plasticity. Furthermore, increased burst firing may be a mechanism through which stress augments extracellular dopamine in selected terminal regions.

Action Potentials↗
PubMed2004

Differential modulation of nociceptive neural responses in medial and lateral pain pathways by peripheral electrical stimulation: a multichannel recording study.

It is well accepted that peripheral electrical stimulation (PES) can produce an analgesic effect in patients with acute and chronic pain. However, the neural basis underlying stimulation-induced analgesia remains unclear. In the present study, we examined the pain-related neural activity modified by peripheral stimulation in rats. The stimulation frequency of pulses applied to needle electrodes in the hindlimb was 2 Hz alternating with 100 Hz, with 0.6 ms pulse width for 2 Hz and 0.2 ms for 100 Hz. The intensity of the stimulation was increased stepwise from 1 to 3 mA with each 1-mA step lasting for 10 min. The nociceptive neural and behavioral responses were examined immediately after the termination of stimulation. Using a multiple-channel recording technique, we simultaneously recorded the activity of many single neurons located in the primary somatosensory and anterior cingulate cortex (ACC), as well as the ventral posterior and medial dorsal thalamus in behaving rats. Our results showed that peripheral electrical stimulation significantly reduced the nociceptive responses in ventroposterior thalamus and somatosensory cortex, indicating an inhibition of nociceptive processing. In contrast, the analgesic stimulation produced a significant increase in mediodorsal thalamus while a less significant decrease in cingulate cortex, reflecting a complicated effect associated with combined antinociceptive activation and nociceptive suppression. These results support the idea that peripheral electrical stimulation can ultimately alter the pain perception by specifically inhibiting the nociceptive transmission in the sensory pathway while mobilizing the antinociceptive action in the affective pathway, thus to produce pain relief.

Animals↗
PubMed2004

High-frequency stimulation of the subthalamic nucleus reverses limb-use asymmetry in rats with unilateral 6-hydroxydopamine lesions.

Deep brain stimulation (DBS) is a widely used clinical treatment for Parkinson's disease (PD). A rodent model of DBS is a necessary tool for understanding the neural mechanisms of this method. Our previous study showed that high-frequency stimulation (HFS) of the subthalamic nucleus (STN) improved treadmill locomotion in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of nigrostriatal dopamine (DA) neurons. The present study tested DBS effects on limb-use asymmetry (LUA) during vertical/lateral exploration in a cylindrical chamber in rats with similar unilateral nigrostriatal DA lesions. Limb-use asymmetry assessment has been used to detect functional capacity over a wide range of dopamine depletion. Before lesioning, rats exhibited regular rearing activity and used both forelimbs equally often to support weight during exploration of the walls of the cylinder. After unilateral nigrostriatal DA lesioning, rats displayed reduced rearing activity and predominant use of the ipsilateral (good) forelimb to touch the wall. HFS of the STN, but not of other nearby regions surrounding the STN, in the lesioned rats restored normal rearing activity and reversed the limb-use asymmetry caused by the unilateral DA depletion. This study is consistent with the possibility that there can be beneficial effects of STN-DBS on behavioral impairments in unilateral DA-depleted rats and may suggest an appropriate rodent model for DBS study.

Animals↗
PubMed2004

Nociceptive responses of anterior cingulate cortical ensembles in behaving rats.

OBJECTIVE: To confirm the role of anterior cingulated cortices (ACC) in the coding of pain affect by exploring the neural ensemble coding pattern within the anterior cingulate cortex in behaving rats with a multichannel recording technique. METHODS: In five adult male Sprague-Dawley rats, two arrays of eight stainless steel microwires were bilaterally implanted into ACC. Noxious radiant heat stimulation was applied to the tail, bilateral fore-paws and hind-paws of freely moving rats. Neuroelectric signals were obtained from the microwires and sent to a multichannel recording device via cables and connectors. The time stamps of neuronal activities were stored on a personal computer for off-line analysis. RESULTS: Noxious heat stimuli evoked predominantly excitatory and sustained neural activity within ACC, reflecting the processing of pain unpleasantness; pain-related anticipatory responses could be seen near the stimulation start, indicating the behavioral preparation for escape; ACC neurons had broad receptive fields by showing quite similar pain-related responses to stimuli on either side of the hind-paw, suggesting that they are not eligible for the localization of a stimulus. CONCLUSION: ACC has played a major role in processing the affective-motivational aspect of pain.

Animals↗
PubMed2003

Parallel pain processing in freely moving rats revealed by distributed neuron recording.

The present study was designed to examine the possible differential roles of the medial and lateral pain systems in pain perception. We used a microwire array recording technique to record the pain-evoked neural activity of multiple neurons in freely moving rats. Noxious radiant heat was delivered to either hind-paw in a randomized order. A total of 256 single units were recorded in primary somatosensory cortex (SI), anterior cingulate cortex (ACC), and medial dorsal (MD) and ventral posterior (VP) thalamus during the painful stimulation. The results showed that SI neurons displayed a strong pain-related excitatory response with short duration and significant contralateral bias; VP had very similar functional patterns to that of SI. This suggested that SI, together with VP, participate in the processing of the sensory-discriminative aspect of pain. In contrast, ACC and MD shared common characteristics of moderate and longer-lasting increase of neural activity, bilateral receptive fields without contralateral preference, as well as the anticipatory response at the start of a painful stimulus, corresponding to the specific role of ACC and MD in the affective-motivational aspects of pain. The results provide an initial demonstration of distributed activity patterns within different pain systems in awake and freely moving rats, hence, providing confirmation of the existence of the dual pain pathways.

Action Potentials↗
PubMed2003

High frequency stimulation of the subthalamic nucleus improves treadmill locomotion in unilateral 6-hydroxydopamine lesioned rats.

This study investigated the influence of electrical stimulation of the subthalamic nucleus (STN) on motor impairment induced by unilateral 6-hydroxydopamine (6-OHDA) lesions in the medial forebrain bundle. Rats were trained to walk on a treadmill and then implanted with microelectrode arrays in and near the STN. The neurotoxin 6-OHDA was injected into the medial forebrain bundle (MFB) unilaterally to produce a targeted lesion of the dopaminergic system. Successful lesions produced impaired treadmill walking behavior. High frequency stimulation (HFS) of the STN improved treadmill walking immediately and restored normal walking patterns. The same HFS failed to evoke visible side effects such as stepping, turning, raising of the head or facial muscle contraction in the absence of treadmill movement, or to change rotational behaviors elicited by the dopamine (DA) agonist apomorphine in unilateral lesioned rats. This suggests that the stimulation did not cause movement by an activation of brainstem locomotor regions or an increase attention leading to movement. Apomorphine-induced rotation may represent an imbalance of dopaminergic activation which remains during HFS. This work may provide a rodent model for deep brain stimulation (DBS) in patients with Parkinson's disease, and be suitable for further investigation of the neural mechanisms underlying the therapeutic effects of DBS.

Animals↗
PubMed2003

Sliding-window technique for the analysis of cerebral evoked potentials.

OBJECTIVE: To evaluate the efficiency of sliding-window technique in extracting and analyzing somatosensory evoked potentials (SEP) from multichannel electroencephalogram (EEG) data. METHODS: A time window of certain window size was moved along the time dimension of data sets. Values within the window were averaged for each trial, and then compared with a preset control window. The probability of randomly appeared significance resulting from repeated statistical comparison was calculated utilizing simulated EEG data sets. Cluster size (number of successive significant data points with given individual significance threshold) was determined to keep the general alpha value under 0.05. To test this procedure, multichannel EEG signals were recorded and analyzed from fourteen healthy right-handed volunteers, with painful and non-painful electrical stimuli delivered to the right middle fingers. RESULTS: Cluster size increased in parallel with window size and individual statistical threshold. The major SEP components of real EEG data, as well as the difference between pain and non-pain SEPs, were demonstrated to be significant with the sliding-window method. CONCLUSION: Sliding-window method is an effective tool for the analysis of SEP data.

Adult↗
PubMed2003

Modulation of pain signal processing by electric acupoint stimulation: an electroencephalogram study.

OBJECTIVE: To investigate the analgesia-related modulation of electroencephalographic activities by transcutaneous electric acupoint stimulation (EAS). METHODS: In 15 healthy human beings, 64-channel electroencephalogram was recorded and power spectrum analysis was employed before, during and after EAS. Non-acupoint electric stimulation was used as control. All subjects were asked to rate their sensation to painful stimulations before and after treatment. RESULTS: The relative theta power near contra-lateral centro-parietal area during EAS was negatively correlated with the pain score after EAS. Similarly, the beta activity during EAS near contra-lateral prefrontal cortex, ipsi-lateral inferior frontal and temporal lobe, and ipsi-lateral occipito-parietal cortex, were all negatively correlated with pain score after EAS. CONCLUSION: These changes might reflect a modulation of brain activity by EAS in specific areas, which were in turn involved in modulation of certain aspects of pain-signal processing.

Acupuncture Points↗
PubMed2003

Effect of baclofen on alcohol and sucrose self-administration in rats.

BACKGROUND: Baclofen, a gamma-aminobutyric acid type B agonist, has been proposed as a pharmacotherapeutic agent in the treatment of addictive disorders such as alcoholism. Preclinical studies documenting the effect of baclofen on alcohol intake have provided conflicting results. The goal of this study was to determine the effect of baclofen pretreatment on ethanol- and sucrose-reinforced responding. METHODS: Animals were trained to self-administer a 10% ethanol in water solution on a fixed ratio 1 schedule of reinforcement by using the sucrose-fade method. With a within-subject design, the effect of three doses of baclofen (1.8, 3.2, and 5.6 mg/kg intraperitoneally) was examined on 10% ethanol- and 2% sucrose-reinforced responding. Dose-dependent effects on responding and on drinking-pattern microstructure were examined. RESULTS: Under a fixed ratio 1 schedule, baclofen reduced responding for alcohol and sucrose reinforcement in a similar, dose-dependent manner. A dose-dependent response attenuation was seen during the initial segment of an operant session when highly repetitive response patterns were generated. Further analysis of drinking ultrastructure revealed that baclofen altered the patterns of these repetitive responses by lengthening the self-initiated intertrial intervals. CONCLUSIONS: Systemic baclofen administration attenuates responding for alcohol and sucrose reinforcement in a dose-dependent manner. If the reinforcing efficacy and response requirement for sucrose and alcohol are matched, then baclofen has similar effects on responding and patterns of drinking microstructure. We conclude that the neural mechanisms that support both ethanol and sucrose self-administration behavior are sensitive to gamma-aminobutyric acid type B modulation.

Alcohol Drinking↗