Input In Rats Research Articles

The Cerebellar Cortex Receives Orofacial Proprioceptive Signals from the Supratrigeminal Nucleus via the Mossy Fiber Pathway in Rats.

Proprioceptive sensory information from muscle spindles is essential for the regulation of motor functions. However, little is known about the motor control regions in the cerebellar cortex that receive proprioceptive signals from muscle spindles distributed throughout the body, including the orofacial muscles. Therefore, in this study, we investigated the pattern of projections in the rat cerebellar cortex derived from the supratrigeminal nucleus (Su5), which conveys orofacial proprioceptive information from jaw-closing muscle spindles (JCMSs). Injections of an anterograde tracer into the Su5 revealed that many bilateral axon terminals (rosettes) were distributed in the granular layer of the cerebellar cortex (including the simple lobule B, crus II and flocculus) in a various sized, multiple patchy pattern. We could also detect JCMS proprioceptive signals in these cerebellar cortical regions, revealing for the first time that they receive muscle proprioceptive inputs in rats. Retrograde tracer injections confirmed that the Su5 directly sends outputs to the cerebellar cortical areas. Furthermore, we injected an anterograde tracer into the external cuneate nucleus (ECu), which receives proprioceptive signals from the forelimb and neck muscle spindles, to distinguish between the Su5- and ECu-derived projections in the cerebellar cortex. The labeled terminals from the ECu were distributed predominantly in the vermis of the cerebellar cortex. Almost no overlap was seen in the terminal distributions of the Su5 and ECu projections. Our findings demonstrate that the rat cerebellar cortex receives orofacial proprioceptive input that is processed differently from the proprioceptive signals from the other regions of the body.

Organization and engagement of a prefrontal-olfactory network during olfactory selective attention.

Sensory perception is profoundly shaped by attention. Attending to an odor strongly regulates if and how it is perceived - yet the brain systems involved in this process are unknown. Here we report integration of the medial prefrontal cortex (mPFC), a collection of brain regions integral to attention, with the olfactory system in the context of selective attention to odors. First, we used tracing methods to establish the tubular striatum (TuS, also known as the olfactory tubercle) as the primary olfactory region to receive direct mPFC input in rats. Next, we recorded (i) local field potentials from the olfactory bulb (OB), mPFC, and TuS, or (ii) sniffing, while rats completed an olfactory selective attention task. Gamma power and coupling of gamma oscillations with theta phase were consistently high as rats flexibly switched their attention to odors. Beta and theta synchrony between mPFC and olfactory regions were elevated as rats switched their attention to odors. Finally, we found that sniffing was consistent despite shifting attentional demands, suggesting that the mPFC-OB theta coherence is independent of changes in active sampling. Together, these findings begin to define an olfactory attention network wherein mPFC activity, as well as that within olfactory regions, are coordinated based upon attentional states.

Distinct roles for motor cortical and thalamic inputs to striatum during motor skill learning and execution.

The acquisition and execution of motor skills are mediated by a distributed motor network, spanning cortical and subcortical brain areas. The sensorimotor striatum is an important cog in this network, yet the roles of its two main inputs, from motor cortex and thalamus, remain largely unknown. To address this, we silenced the inputs in rats trained on a task that results in highly stereotyped and idiosyncratic movement patterns. While striatal-projecting motor cortex neurons were critical for learning these skills, silencing this pathway after learning had no effect on performance. In contrast, silencing striatal-projecting thalamus neurons disrupted the execution of the learned skills, causing rats to revert to species-typical pressing behaviors and preventing them from relearning the task. These results show distinct roles for motor cortex and thalamus in the learning and execution of motor skills and suggest that their interaction in the striatum underlies experience-dependent changes in subcortical motor circuits.

Imipramine ameliorates early life stress-induced alterations in synaptic plasticity in the rat lateral amygdala

Long-term potentiation (LTP) and long-term depression (LTD) are two opposite forms of synaptic plasticity at the cortical and thalamic inputs to the lateral amygdala (LA). It has been demonstrated that maternal separation (MS) of rat pups results in alterations in the potential for both pathways to undergo LTP and LTD in adolescence. Imipramine, a prototypic tricyclic antidepressant, has been shown to counteract some detrimental effects of MS on rat behavior, however it is not known whether MS-induced alterations in the potential for bidirectional synaptic plasticity in the LA could be reversed by imipramine treatment. To this end, rat pups were subjected to MS (3h/day) on postnatal days (PNDs) 1–21. On each of PNDs 29–42, male rats previously subjected to MS were injected subcutaneously with imipramine (10mg/kg). Field potentials were recorded ex vivo from slices containing the LA and saturating levels of LTP and LTD were induced. At the thalamic input to the LA, both the maximum LTP and the maximum LTD were reduced in rats subjected to MS when compared to control animals, confirming earlier results. However, these effects were no longer present in rats subjected to MS and later treated with imipramine. At the cortical input in slices prepared from MS-subjected rats, an impairment of the maximum LTP and an enhancement of the maximum LTD were observed. At the cortical input in rats subjected to MS and receiving imipramine treatment, the level of LTD was comparable to control but imipramine did not restore the potential for LTP at this input. These results demonstrate that imipramine fully reverses the effects of MS in the thalamo-amygdalar pathway, however, in the cortico-amygdalar pathway the reversal of the effects of MS by imipramine is partial.

ATP-sensitive muscle afferents activate spinal trigeminal neurons with meningeal afferent input in rat - pathophysiological implications for tension-type headache.

BackgroundTension-type headache and other primary headaches may be triggered or aggravated by disorders of pericranial muscles, which is possibly due to convergent or collateral afferent input from meningeal and muscular receptive areas. In rodent models high extracellular concentrations of ATP caused muscle nociception and central sensitization of second order neurons. In a rat model of meningeal nociception we asked if spinal trigeminal activity induced by ATP can be modulated by local anaesthesia of distinct muscles.MethodsOngoing activity was recorded from spinal trigeminal neurons with afferent input from the cranial dura mater, the temporal muscle and neck muscles. The stable ATP analogue α,β-methylene adenosine 5′-triphosphate (α,β-meATP, 10 mM) was injected into the ipsilateral temporal muscle, 30 min later followed by injection of local anaesthetics (lidocaine, 2 %) into the ipsilateral neck muscles and/or the temporal muscle.ResultsInjection of α,β-meATP into the temporal muscle caused progressive increase in ongoing activity of most of the spinal trigeminal neurons within 30 min. Injection of lidocaine into the neck muscles and/or the temporal muscle reduced this activation to previous levels within 10 min.ConclusionsDistinct spinal trigeminal neurons processing meningeal nociceptive information are under the control of convergent afferent input from several pericranial muscles. Blockade of at least one of these inputs can normalize central trigeminal activity. This may explain why therapeutic manipulations of head muscles can be beneficial in primary headaches.

Hippocampal state-dependent behavioral reflex to an identical sensory input in rats.

We examined the local field potential of the hippocampus to monitor brain states during a conditional discrimination task, in order to elucidate the relationship between ongoing brain states and a conditioned motor reflex. Five 10-week-old Wistar/ST male rats underwent a serial feature positive conditional discrimination task in eyeblink conditioning using a preceding light stimulus as a conditional cue for reinforced trials. In this task, a 2-s light stimulus signaled that the following 350-ms tone (conditioned stimulus) was reinforced with a co-terminating 100-ms periorbital electrical shock. The interval between the end of conditional cue and the onset of the conditioned stimulus was 4±1 s. The conditioned stimulus was not reinforced when the light was not presented. Animals successfully utilized the light stimulus as a conditional cue to drive differential responses to the identical conditioned stimulus. We found that presentation of the conditional cue elicited hippocampal theta oscillations, which persisted during the interval of conditional cue and the conditioned stimulus. Moreover, expression of the conditioned response to the tone (conditioned stimulus) was correlated with the appearance of theta oscillations immediately before the conditioned stimulus. These data support hippocampal involvement in the network underlying a conditional discrimination task in eyeblink conditioning. They also suggest that the preceding hippocampal activity can determine information processing of the tone stimulus in the cerebellum and its associated circuits.

Unilateral whisker trimming in newborn rats alters neuronal coincident discharge among mature barrel cortex neurons

It is known that sensory deprivation, including postnatal whisker trimming, can lead to severe deficits in the firing rate properties of cortical neurons. Recent results indicate that development of synchronous discharge among cortical neurons is also activity influenced, and that correlated discharge is significantly impaired following loss of bilateral sensory input in rats. Here we investigate whether unilateral whisker trimming (unilateral deprivation or UD) after birth interferes in the same way with the development of synchronous discharge in cortex. We measured the coincidence of spikes among pairs of neurons recorded under urethane anesthesia in one whisker barrel field deprived by trimming all contralateral whiskers for 60 days after birth (UD), and in untrimmed controls (CON). In the septal columns around barrels, UD significantly increased the coincident discharge among cortical neurons compared with CON, most notably in layers II/III. In contrast, synchronous discharge was normal between layer IV UD barrel neurons: i.e., not different from CON. Thus, while bilateral whisker deprivation (BD) produced a global deficit in the development of synchrony in layer IV, UD did not block the development of synchrony between neurons in layer IV barrels and increased synchrony within septal circuits. We conclude that changes in synchronous discharge after UD are unexpectedly different from those recorded after BD, and we speculate that this effect may be due to the driven activity from active commissural inputs arising from the contralateral hemisphere that received normal activity levels during postnatal development.

MP47-14 PIOGLITAZONE IS PROTECTIVE AGAINST POST-PROSTATECTOMY ERECTILE DYSFUNCTION

INTRODUCTION AND OBJECTIVES: Penile smooth muscle tone is finely tuned by neurogenic stimuli. Alteration of neurogenic regulation could cause an imbalance in favour of contractile stimuli and compromise erection. We have previously observed that calcium-activated potassium channel (KCa) stimulation enhances vasodilatory capacity of PDE5 inhibitors in human penile arteries. The aim of this work was to evaluate the impact of KCa modulation on the neurogenic regulation of cavernosal smooth muscle tone in rats and humans. METHODS: Rat corpus cavernosum (RCC) was obtained from thirty 12-16 weeks old male Sprague-Dawley rats. Human corpus cavernosum (HCC) strips were obtained from 20 patients with erectile dysfunction (ED) who gave informed consent at the time of penile prosthesis implantation. RCC and HCC were mounted in organ chambers and responses to electrical field stimulation (EFS) were evaluated. RESULTS: EFS caused reproducible, frequency-dependent contractions in RCC. Blockade of KCa with tertaethylammonium (TEA) markedly potentiated neurogenic contractions (16Hz, 67.2 3.2% vs. 105.6 4.6% at 5mM, p<0.001) but did not modify norepinephrineinduced contractions. By using specific KCa subtype blockers, largeconductance KCa (BK) appeared as responsible for modulation of neurogenic contractions. Stimulation of BK with NS1619 significantly inhibited EFS-induced contractions in RCC (67.5 5.4% vs. 39.3 5.8%, p<0.01 at 30mM). BK stimulation also caused a significant potentiation of EFS-induced relaxations in phenylephrine-contracted RCC treated with guanethidine and atropine (2 Hz, 31.8 6.9% vs. 64.9 6.7%, p<0.01). Similar results were obtained in HCC where TEA caused concentration-dependent enhancement of EFS-induced contractions (35.3 3.4% vs. 118.5 32.0% at 5mM, p<0.01) while BK activation with NS1619 (30mM) inhibited neurogenic contractions and potentiated neurogenic relaxations. CONCLUSIONS: BK participates in regulation of neurogenic control of cavernosal smooth muscle tone. Pharmacological stimulation of these channel would favor relaxant responses over contractile input in rat and human cavernosal tissue. Thus, BK stimulation could be a reasonable strategy for treating ED mainly in situations involving imbalanced regulation of neurogenic control.

MP47-13 CALCIUM-ACTIVATED POTASSIUM CHANNEL (KCA) STIMULATION MODULATES NEUROGENIC CONTRACTION AND FAVOURS NEUROGENIC RELAXATION IN RAT AND HUMAN CORPUS CAVERNOSUM

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 2014MP47-13 CALCIUM-ACTIVATED POTASSIUM CHANNEL (KCA) STIMULATION MODULATES NEUROGENIC CONTRACTION AND FAVOURS NEUROGENIC RELAXATION IN RAT AND HUMAN CORPUS CAVERNOSUM Juan I. Martínez-Salamanca, José M. La Fuente, Argentina Fernández, Eduardo Martínez-Salamanca, Joaquín Carballido, and Javier Angulo Juan I. Martínez-SalamancaJuan I. Martínez-Salamanca More articles by this author , José M. La FuenteJosé M. La Fuente More articles by this author , Argentina FernándezArgentina Fernández More articles by this author , Eduardo Martínez-SalamancaEduardo Martínez-Salamanca More articles by this author , Joaquín CarballidoJoaquín Carballido More articles by this author , and Javier AnguloJavier Angulo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1466AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Penile smooth muscle tone is finely tuned by neurogenic stimuli. Alteration of neurogenic regulation could cause an imbalance in favour of contractile stimuli and compromise erection. We have previously observed that calcium-activated potassium channel (KCa) stimulation enhances vasodilatory capacity of PDE5 inhibitors in human penile arteries. The aim of this work was to evaluate the impact of KCa modulation on the neurogenic regulation of cavernosal smooth muscle tone in rats and humans. Methods Rat corpus cavernosum (RCC) was obtained from thirty 12-16 weeks old male Sprague-Dawley rats. Human corpus cavernosum (HCC) strips were obtained from 20 patients with erectile dysfunction (ED) who gave informed consent at the time of penile prosthesis implantation. RCC and HCC were mounted in organ chambers and responses to electrical field stimulation (EFS) were evaluated. Results EFS caused reproducible, frequency-dependent contractions in RCC. Blockade of KCa with tertaethylammonium (TEA) markedly potentiated neurogenic contractions (16Hz, 67.2±3.2% vs. 105.6±4.6% at 5mM, p<0.001) but did not modify norepinephrine-induced contractions. By using specific KCa subtype blockers, large-conductance KCa (BK) appeared as responsible for modulation of neurogenic contractions. Stimulation of BK with NS1619 significantly inhibited EFS-induced contractions in RCC (67.5±5.4% vs. 39.3±5.8%, p<0.01 at 30μM). BK stimulation also caused a significant potentiation of EFS-induced relaxations in phenylephrine-contracted RCC treated with guanethidine and atropine (2 Hz, 31.8±6.9% vs. 64.9±6.7%, p<0.01). Similar results were obtained in HCC where TEA caused concentration-dependent enhancement of EFS-induced contractions (35.3±3.4% vs. 118.5±32.0% at 5mM, p<0.01) while BK activation with NS1619 (30μM) inhibited neurogenic contractions and potentiated neurogenic relaxations. Conclusions BK participates in regulation of neurogenic control of cavernosal smooth muscle tone. Pharmacological stimulation of these channel would favor relaxant responses over contractile input in rat and human cavernosal tissue. Thus, BK stimulation could be a reasonable strategy for treating ED mainly in situations involving imbalanced regulation of neurogenic control. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e523 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Juan I. Martínez-Salamanca More articles by this author José M. La Fuente More articles by this author Argentina Fernández More articles by this author Eduardo Martínez-Salamanca More articles by this author Joaquín Carballido More articles by this author Javier Angulo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Ultradian corticosterone secretion is maintained in the absence of circadian cues

Plasma levels of corticosterone exhibit both circadian and ultradian rhythms. The circadian component of these rhythms is regulated by the suprachiasmatic nucleus (SCN). Our studies investigate the importance of the SCN in regulating ultradian rhythmicity. Two approaches were used to dissociate the hypothalamic-pituitary-adrenal (HPA) axis from normal circadian input in rats: (i) exposure to a constant light (LL) environment and (ii) electrolytic lesioning of the SCN. Blood was sampled using an automated sampling system. As expected, both treatments resulted in a loss of the circadian pattern of corticosterone secretion. Ultradian pulsatile secretion of corticosterone however, was maintained across the 24 h in all animals. Furthermore, the loss of SCN input revealed an underlying relationship between locomotor and HPA activity. In control (LD) rats there was no clear correlation between ultradian locomotor activity and hormone secretion, whereas, in LL rats, episodes of ultradian activity were consistently followed by periods of increased pulsatile hormone secretion. These data clearly demonstrate that the ultradian rhythm of corticosterone secretion is generated through a mechanism independent of the SCN input, supporting recent evidence for a sub-hypothalamic pulse generator.

CB1 Cannabinoid Receptor Expression in the Striatum: Association with Corticostriatal Circuits and Developmental Regulation

Corticostriatal circuits mediate various aspects of goal-directed behavior and are critically important for basal ganglia-related disorders. Activity in these circuits is regulated by the endocannabinoid system via stimulation of CB1 cannabinoid receptors. CB1 receptors are highly expressed in projection neurons and select interneurons of the striatum, but expression levels vary considerably between different striatal regions (functional domains). We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors defined by their cortical inputs in rats. We also assessed changes in CB1 expression in the striatum during development. Our results show that CB1 expression is highest in juveniles (P25) and then progressively decreases toward adolescent (P40) and adult (P70) levels. At every age, CB1 receptors are predominantly expressed in sensorimotor striatal sectors, with considerably lower expression in associative and limbic sectors. Moreover, for most corticostriatal circuits there is an inverse relationship between cortical and striatal expression levels. Thus, striatal sectors with high CB1 expression (sensorimotor sectors) tend to receive inputs from cortical areas with low expression, while striatal sectors with low expression (associative/limbic sectors) receive inputs from cortical regions with higher expression (medial prefrontal cortex). In so far as CB1 mRNA levels reflect receptor function, our findings suggest differential CB1 signaling between different developmental stages and between sensorimotor and associative/limbic circuits. The regional distribution of CB1 receptor expression in the striatum further suggests that, in sensorimotor sectors, CB1 receptors mostly regulate GABA inputs from local axon collaterals of projection neurons, whereas in associative/limbic sectors, CB1 regulation of GABA inputs from interneurons and glutamate inputs may be more important.

Characterization of upper thoracic spinal neurons receiving noxious cardiac and/or somatic inputs in diabetic rats

The aim of the present study was to examine spinal processing of cardiac and somatic nociceptive input in rats with STZ-induced diabetes.Type 1 diabetes was induced with streptozotocin (50mg/kg) in 14 male Sprague–Dawley rats and citrate buffer was injected in 14 control rats. After 4–11weeks, the rats were anesthetized with pentobarbital, ventilated and paralyzed. A laminectomy enabled extracellular recording of T3 spinal cord neuronal activity. Intrapericardial administration of a mixture of algogenic chemicals (bradykinin, serotonin, prostaglandin E2 (all at 10−5M), and adenosine (10−3M)) was applied to activate nociceptors of cardiac afferent nerve endings. Furthermore, somatic receptive properties were examined by applying innocuous (brush and light pressure) and noxious (pinch) cutaneous mechanical stimuli.Diabetes-induced increases in spontaneous activity were observed in subsets of neurons exhibiting long-lasting excitatory responses to administration of the algogenic mixture.Algogenic chemicals altered activity of a larger proportion of neurons from diabetic animals (73/111) than control animals (55/115, P<0.05). Some subtypes of neurons exhibiting long-lasting excitatory responses, elicited prolonged duration and others, had a shortened latency. Some neurons exhibiting short-lasting excitatory responses in diabetic animals elicited a shorter latency and some a decreased excitatory change. The size of the somatic receptive field was increased for cardiosomatic neurons from diabetic animals. Cutaneous somatic mechanical stimulation caused spinal neurons to respond with a mixture of hyper- and hypoexcitability.In conclusion, diabetes induced changes in the spinal processing of cardiac input and these might contribute to cardiovascular autonomic neuropathy in patients with diabetes.

Comparison of activity characteristics of the cuneate nucleus and thoracic spinal neurons receiving noxious cardiac and/or somatic inputs in rats

Previous studies have shown that the gracile nucleus in postsynaptic dorsal column pathway plays an important role in conveying nociceptive information from pelvic visceral organs. The purpose of this study was to compare effects of a noxious cardiac stimulus on neuronal activity in the cuneate nucleus and upper thoracic spinal cord in rats. Extracellular potentials of single neurons in the cuneate nucleus and upper thoracic (T3) spinal cord were recorded in pentobarbital anesthetized, ventilated and paralyzed male rats. To activate cardiac nociceptors, a silicone tube was placed in the pericardial sac over the left ventricle to administer a solution of bradykinin (10 μg/ml, 0.2 ml, 1 min). The number of cuneate neurons responding to intrapericardial bradykinin (IB, 15.6%, 17/109) was significantly less than for T3 neurons (43.2%, 48/111, P < 0.05). IB excited 9/17 (52.9%) cuneate neurons and inhibited eight neurons. In contrast, IB excited a significantly higher percentage of responding spinal neurons than those in cuneate nucleus (43/48, 89.6%, P < 0.01). The ratio of short latency/long-lasting responses of cuneate neurons to IB (14/3) were significant higher than responses of spinal neurons (26/22, P < 0.05). Spontaneous activity (5.5 ± 0.7 imp/s), response amplitudes (6.0 ± 0.6 imp/s) and durations (83.4 ± 10.8 sec) of cuneate neurons excited by IB were significantly less than for spinal neurons (11.5 ± 1.3 imp/s, 20.4 ± 2.0 imp/s and 104.9 ± 7.0 imp/s, P < 0.01, P < 0.01, P < 0.05), respectively. These results indicate that the cuneate nucleus neurons play a relatively minor role in transmission of cardiac nociceptive information in comparison to upper thoracic spinal neurons.

Cross-organ sensitization of thoracic spinal neurons receiving noxious cardiac input in rats with gastroesophageal reflux

Gastroesophageal reflux (GER) frequently triggers or worsens cardiac pain or symptoms in patients with coronary heart disease. This study aimed to determine whether GER enhances the activity of upper thoracic spinal neurons receiving noxious cardiac input. Gastric fundus and pyloric ligations as well as a longitudinal myelotomy at the gastroesophageal junction induced acute GER in pentobarbital-anesthetized, paralyzed, and ventilated male Sprague-Dawley rats. Manual manipulations of the stomach and lower esophagus were used as surgical controls in another group. At 4-9 h after GER surgery, extracellular potentials of single neurons were recorded from the T3 spinal segment. Intrapericardial bradykinin (IB) (10 microg/ml, 0.2 ml, 1 min) injections were used to activate cardiac nociceptors, and esophageal distensions were used to activate esophageal afferent fibers. Significantly more spinal neurons in the GER group responded to IB compared with the control group (69.1 vs. 38%, P < 0.01). The proportion of IB-responsive neurons in the superficial laminae of GER animals was significantly different from those in deeper layers (1/8 vs. 46/60, P < 0.01); no difference was found in control animals (7/25 vs. 20/46, P > 0.05). Excitatory responses of spinal neurons to IB in the GER group were greater than in the control group [32.4 +/- 3.5 impulses (imp)/s vs. 13.3 +/- 2.3 imp/s, P < 0.01]. Forty-five of 47 (95.7%) neurons responded to cardiac input and ED, which was higher than the control group (61.5%, P < 0.01). These results indicate that acute GER enhanced the excitatory responses of thoracic spinal neurons in deeper laminae of the dorsal horn to noxious cardiac stimulus.

Somatic afferent modulation of thoracic (T9-T10) spinal neurons receiving gastric mechanical input in rats

The aim was to determine whether somatic afferent fiber stimulation influences thoracic spinal neuronal activity responding to gastric distensions. Extracellular potentials of single T9-T10 spinal neurons were recorded in anesthetized male rats. Ipsilateral median and peroneal nerve afferent stimulation (MNAS, PNAS) was delivered by electrodes. Inflation of a latex balloon was used to produce gastric distension. MNAS and PNAS (1.5 mA, 50 Hz, 10 sec) altered activity of 63% and 66% of the spinal neurons excited or inhibited by gastric distension, respectively. MNAS more frequently reduced spinal neuronal activity with excitatory responses to gastric distension than did PNAS (p < 0.05). PNAS more likely increased neuronal activity with low-threshold excitatory responses to gastric distension than MNAS (p < 0.05). Peripheral somatic afferent information utilizes central pathways to modulate gastric afferent processing in T9-T10 spinal neurons. Thus, somatic afferent stimulation might be used to treat gastric pain and/or hypersensitivity.

Central Lateral Thalamic Neurons Receive Noxious Visceral Mechanical and Chemical Input in Rats

Thalamic intralaminar and medial nuclei participate mainly in affective and motivational aspects of pain processing. Unique to the present study were identification and characterization of spontaneously active neurons in the central lateral nucleus (CL) of the intralaminar thalamus, which were found to respond only to viscerally evoked noxious stimuli in animals under pentobarbital anesthesia. Responses to noxious colorectal distention, intrapancreatic bradykinin, intraperitoneal dilute acetic acid, and greater splanchnic nerve electrical stimulation were characterized. Electrophysiological recordings revealed activity in most CL neurons (93%) was excited (69%) or inhibited (31%) in response to noxious visceral stimulation of visceral nerves. Expression of c-Fos observed in CL nucleus after intensive visceral stimulation confirmed the activation. However, excited CL neurons did not have somatic fields, except in 3 of 43 (7%) CL neurons tested for responses to somatic stimulation (innocuous brush and noxious pinch). Intrathecal administration of morphine significantly reduced the increased responses of CL neurons to colorectal and pancreatic stimuli and was naloxone reversible. High-level thoracic midline dorsal column (DC) myelotomy also dramatically reduced responses, identifying the DC as a major route of travel from the spinal cord for CL input, in addition to input traveling ventromedially in the spinothalamic tract identified anatomically in a previous study. Spinal cord and lower brain stem cells providing input to medial thalamus were mapped after stereotaxic injections of a retrograde dye. These data combined with our previous data suggest that the CL nucleus is an important component of a medial visceral nociceptive system that may mediate attentional, affective, endocrine, motor, and autonomic responses to noxious visceral stimuli.

Activation of NMDA Receptor is Associated with Up-regulation of COX-2 Expression in the Spinal Dorsal Horn during Nociceptive Inputs in Rats

Cyclooxygenases-2 (COX-2) in the spinal dorsal horn is up-regulated and plays an important role in pain and hyperalgesia induced by nociceptive stimulation. The mechanisms involved in the up-regulation of spinal COX-2 during nociceptive stimulation are yet not well understood. Because the important role of NMDA and its receptor in transmission of nociceptive information in the spinal cord, activation of the spinal NMDA receptor might contribute to the up-regulation of spinal COX-2 expression. The present study was undertaken to demonstrate the above hypothesis by observing changes of COX-2 expression in the spinal dorsal horn in rats subjected to formalin test and intrathecal administration of NMDA, a selective NMDA receptor agonist, in conditions with or without presence of MK-801, an antagonist of NMDA receptor, using methods of Western blotting, reverse transcription polymerase chain reaction and immunohistochemistry. The results showed that intrathecal injection of MK-801, a noncompetitive antagonist of NMDA receptor, significantly suppressed the up-regulation of the COX-2 expression and characteristic pain behavior responses evoked in formalin test. Whereas, intrathecal injection of NMDA significantly up-regulated the expression of COX-2 in the spinal dorsal horn in a time course corresponding to that of nociceptive behavioral responses elicited by the intrathecal NMDA administration. In addition, the up-regulation of the COX-2 expression induced by the intrathecal NMDA was dose-dependent and blocked by prior administration of MK-801. These findings proved that activation of NMDA receptor is associated with the up-regulation of COX-2 expression in the spinal dorsal horn during nociceptive stimulation in rats.

S1820 Somatic Afferent Modulation of Thoracic (T9-T10) Spinal Neurons Receiving Gastric Mechanical Input in Rats

S1820 Somatic Afferent Modulation of Thoracic (T9-T10) Spinal Neurons Receiving Gastric Mechanical Input in Rats

Distinct changes in evoked and resting globus pallidus activity in early and late Parkinson's disease experimental models

The main clinical manifestations of Parkinson's disease are caused by alterations of basal ganglia activity that are tied in with the progressive loss of mesencephalic dopaminergic neurons. Recent theoretical and modeling studies have suggested that changes in resting neuronal activity occurred later in the course of the disease than those evoked by phasic cortical input. However, there is no empirical support for this proposal. Here we report a marked increase in the responsiveness of globus pallidus neurons to electrical motor cortex stimulation, in the absence of noticeable changes in resting activity, in anesthetized rats that had consistently shown a deficit in forelimb use during behavioral testing before the experiments, and had approximately 45% dopamine neurons spared in the substantia nigra. Pallidal neurons were also over-responsive to motor cortex stimulation and lost spatial selectivity for cortical inputs in rats with extensive nigrostriatal damage. After partial lesions, over-responsiveness was mainly due to an increased proportion of neurons showing excitatory responses, while extensive lesions led to an increased likelihood of inhibitory responding neurons. Changes in resting neuronal activity, comprising pauses disrupting tonic discharge, occurred across different global brain states, including an activated condition which shares similarities with natural patterns of cortical activity seen in awake states and rapid eye-movement sleep, but only after massive nigrostriatal degeneration. These results suggest that a loss of functional segregation and an abnormal temporal encoding of phasic cortical inputs by globus pallidus neurons may contribute to inducing early motor impairment in Parkinson's disease.

Inhalation of a pulmonary irritant modulates activity of lumbosacral spinal neurons receiving colonic input in rats

The purpose of the present study was to determine whether an intraspinal nociceptive pathway from the lungs modulated activity of spinal neurons that also received afferent input from the colon. Extracellular potentials of single lumbosacral (L6-S2) spinal neurons were recorded in pentobarbital-anesthetized, paralyzed, and ventilated male rats. The lower airways and lungs were irritated by injecting ammonia vapor over a 30% NH(4)OH solution into the inspiratory line of the ventilator (0.5 ml, 20 s). Graded colorectal distension (CRD; 20-60 mmHg, 20 s) was produced by air inflation of a balloon. Inhaled ammonia (IA) altered activity of 31/51 (61%) lumbosacral spinal neurons responding to noxious CRD (60 mmHg, 20 s). In contrast, IA changed activity of 3/30 (10%) spinal neurons with somatic fields that did not respond to colorectal inputs. IA decreased activity of 16/31 (52%) spinal neurons and increased activity of the other 15 neurons with colorectal input. Multiple patterns of viscerovisceral convergent spinal neurons with excitatory and inhibitory responses to CRD and IA were observed; 87% (27/31) of the viscerovisceral convergent neurons also responded to innocuous and/or noxious stimuli of somatic fields. Bilateral cervical vagotomy abolished responses to IA in 2/8 tested neurons, indicating that the remaining 6 neurons had input originating from sympathetic afferent fibers. Rostral C1 spinal transection did not abolish inhibitory responses to IA in 4/4 neurons, but L2 transection eliminated inhibitory responses to IA in 3/3 neurons. These results indicated that irritation of the lower airways modulated activity of lumbosacral spinal neurons with colorectal input. It might contribute to intraspinal cross talk between the colon and lungs.