Paracentral Thalamic Nuclei Research Articles

CB1-cannabinoid-, TRPV1-vanilloid- and NMDA-glutamatergic-receptor-signalling systems interact in the prelimbic cerebral cortex to control neuropathic pain symptoms

Neuropathic pain (NP) is a challenge due to our limited understanding of the mechanisms that initiate and maintain chronic pain. The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is an important area of the emotional and cognitive components of pain and pharmacological systems can interact into the neocortex to elaborate the chronic pain. This work aimed to investigate the pharmacological cross-talk between synaptic neurotransmission, neuroanatomical approaches and NP conditions. A bidirectional neural tract tracer, the 3000-molecular-weight biodextran (BDA) was microinjected into the PrL cortex. The mechanical withdrawal threshold (MWT) was recorded by a von Frey test, and the effect of prelimbic cortex CB1, NMDA, and TRPV1 receptor modulation was evaluated 21 days after chronic constriction injury (CCI) of the sciatic nerve in male Wistar rats. Microinjection of a bidirectional neurotracer in the PrL cortex showed connections with the lateral division of the mediodorsal thalamic nucleus (MDL), central division of the mediodorsal thalamic nucleus (MDC), centrolateral thalamic nucleus (CL), ventromedial thalamic nucleus (VM), and the paracentral thalamic nucleus (PC). In detail, AM251, a CB1 receptor antagonist (at 50, 100 and 200 pmol) microinjections intra-PrL cortex decreased the MWT. Administrations of 6-iodonordihydrocapsaicin (6-I-CPS), a transient receptor potential vanilloid type 1 (TRPV1) antagonist, at 3 nmol and the endocannabinoid anandamide (AEA) at 50 and 100 pmol increased the MWT. AEA at 200 pmol injected in the PrL cortex decreased the MWT, and this hyperalgesic effect was blocked by 6-I-CPS at 3 nmol. The AEA (at 100 pmol) anti-allodynic effect was attenuated by AM251 (at 5 pmol). The TRPV1 selective agonist N-oleoyldopamine (OLDA) at 10 μM decreased the MWT. The blockade of the NMDA receptor with LY235959 (at 8 nmol) and 6-I-CPS (at 3 nmol) reversed the OLDA (at 10 μM) hyperalgesic effect. These findings showed that the PrL cortex sends pathways to thalamic nuclei that can mediate the nociception. We also suggest that the PrL cortex is involved in the potentiation and maintenance of mechanical allodynia by NMDA and TRPV1 receptor activation and that attenuation of this allodynia depends on CB1 receptor activation during NP.

Ascending parabrachio-thalamo-striatal pathways: Potential circuits for integration of gustatory and oral motor functions

The medial parabrachial nucleus (MPB) and external part of the medial parabrachial nucleus (MPBE) relay gustatory, oral mechanosensory and other visceral information in the rat brain and reportedly project not only to the parvicellular part of the posteromedial ventral thalamic nucleus (VPMpc) but also to the ventrocaudal part of the intralaminar thalamic nuclei. Generally, the intralaminar thalamic nuclei project topographically to the caudate putamen (CPu); however, it is unclear where the ventrocaudal part of the intralaminar thalamic nuclei projects within the CPu. Thus, we visualized neural pathways from the MPB and MPBE to the CPu via the ventrocaudal part of the intralaminar thalamic nuclei using an anterograde tracer, biotinylated dextran amine, and a retrograde tracer, cholera toxin B subunit. We found that the MPB and MPBE sent a relatively stronger input to the ventrocaudal part of the intralaminar thalamic nuclei such as the oval paracentral thalamic nucleus (OPC), central medial thalamic nucleus (CM) and parafascicular thalamic nucleus (PF) and retroreuniens area (RRe) as compared to the VPMpc. In turn, these thalamic nuclei projected to the ventral part of the CPu with the topographical arrangement as follows: the OPC to the ventrocentral part of the CPu; ventrolateral part of the PF to the ventrolateral part of the CPu; and the caudal part of the CM, ventromedial part of the PF and RRe to the ventromedial part of the CPu. Further, we found that the VPMpc rather projected to the interstitial nucleus of the posterior limb of the anterior commissure than the CPu. The ventral part of the CPu is reported to be involved in jaw movement as well as food and water intake functions. Therefore, these parabrachio-thalamo-striatal pathways that we demonstrated here suggest that gustatory and oral mechanosensory information affects feeding behavior within the ventral part of the CPu.

Formalin-induced pain and μ-opioid receptor density in brain and spinal cord are modulated by A 1 and A 2a adenosine agonists in mice

The effects of adenosine analogues on pain have been shown to depend on the subtype receptor involved as well as on the nociceptive stimuli and on the route of administration. In the first experiment of the present study intraperitoneal administration of the A 1 receptor agonist N 6-cyclopentyladenosine (CPA) (0.015, 0.03, 0.09, 0.15, 0.21, 0.3 mg/kg) induced dose-dependent analgesia to formalin pain in both phases characterizing the test. The A 2a receptor agonist 2-[p-2-(carbonyl-ethyl)-phenyethylamino]-5′- N-ethylcarboxaminoadenosine (CGS21680) (0.025, 0.05, 0.1, 0.15 mg/kg) significantly affected behavioral responses to formalin only during the early phase. In the second experiment the interaction between adenosine and the opioid system was investigated through both behavioral and neurochemical studies. The opioid antagonist naltrexone (0.1 mg/kg) did not affect the antinociception induced by CPA (0.21 mg/kg) and CGS21680 (0.05 mg/kg). Autoradiographic studies showed that formalin administration significantly modified μ-opioid receptor density in the superficial laminae of the spinal cord and in the paracentral thalamic nucleus, contralateral to the side of formalin injection. CPA and CGS21680 counteracted these effects induced by formalin. In conclusion the present study confirms and extends the role of A 1 and A 2a adenosine receptors in the modulation of inflammatory pain and their interaction with the μ-opioid system, and suggests further investigation of these purinergic receptors from a therapeutic perspective.

Contribution of intralaminar thalamic nuclei to spike-and-wave-discharges during spontaneous seizures in a genetic rat model of absence epilepsy.

In an epileptic rat model of generalized absence epilepsies, the genetic absence epilepsy rats from Strasbourg (GAERS), simultaneous recordings of bilateral epidural electroencephalogram (EEG) of the prefrontal cortex and unit activity of neurons in the intralaminar centrolateral (CL) and paracentral thalamic nucleus (PC) were performed under neurolept-anaesthesia (fentanyl-dehydrobenzperidol analgesia). Spike-and-wave (SW) seizures in these rats are characterized by generalized 7-10 Hz spike-and-wave discharges (SWDs) on the EEG. All neurons recorded in intralaminar thalamic nuclei during spontaneous SWDs showed high-frequency (average 368 Hz, range 200-500 Hz), burst-like activity, which occurred in a highly synchronized fashion with every SWD or with alternating SWD-complexes. Burst discharges in intralaminar neurons were delayed by 13.1 ms (CL) and 12.7 ms (PC), with respect to the spike component of a given SWD on the EEG, whereas burst discharges in the ventrobasal thalamus (VB) and in the rostral nucleus reticularis thalami (rRT) preceded the spike component by 17.8 ms and 8.3 ms, respectively. The onset of SWDs on the EEG was preceded by a tonic firing pattern (20-50 Hz) in about one third of CL and PC neurons. Microiontophoretic application of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline aggravated, whereas, the glutamate receptor antagonists DNQX and APV dampened, SWD-related discharges in PC and CL; the GABAB receptor antagonist CGP 35347 had no measurable effect. These data indicate that intrathalamic nuclei are recruited rhythmically during SWDs, through mechanisms that seem to rely on a delayed glutamatergic excitation modulated by GABAergic influences, rather than a GABA-mediated rebound burst activity typical of relay cells. The finding of a temporal delay of SWD-related activity in intrathalamic, compared with "specific" thalamic relay nuclei, does not support the notion of a leading or pacemaker role in SWD generation. It is, however, rather suggestive of a function of intrathalamic neurons during synchronization and maintenance of neuronal oscillations, and these intrathalamic neurons may be recruited through glutamatergic corticofugal inputs.

Parabrachial Internal Lateral Neurons Convey Nociceptive Messages from the Deep Laminas of the Dorsal Horn to the Intralaminar Thalamus

This study investigates the physiological properties of parabrachial internal lateral (PBil) neurons that project to the paracentral thalamic (PC) nucleus using antidromic activation and single-unit recording techniques in anesthetized rat. We reported here that most of these neurons responded exclusively to the nociceptive stimulation of large receptive fields with a sustained firing that often outlasted the stimulus up to several minutes. These responses were depressed by intravenous morphine. Our results demonstrated a novel spino-PBil-PC pathway, which transmits nociceptive messages to the PC nucleus, which in turn projects to the prefrontal cortex. Recent clinical imaging studies showed the important participation of prefrontal cortex in emotional response to pain. This spino-PBil-PC pathway may explain how nociceptive messages reach the prefrontal cortex and thus trigger unbearable aversive aspects of pain.

Parabrachial nucleus projections to midline and intralaminar thalamic nuclei of the rat.

The projections from the parabrachial nucleus to the midline and intralaminar thalamic nuclei were examined in the rat. Stereotaxic injections of the retrograde tracer cholera toxin-beta (CTb) were made in each of the intralaminar nuclei of the dorsal thalamus (the lateral parafascicular, medial parafascicular, oval paracentral, central lateral, paracentral, and central medial nuclei), as well as the midline thalamic nuclei (the paraventricular, intermediodorsal, mediodorsal, paratenial, rhomboid, reuniens, parvicellular part of the ventral posterior, and caudal ventral medial nuclei). The retrograde cell body labeling pattern within the parabrachial subnuclei was then analyzed. The paracentral thalamic nucleus received an input only from the internal lateral parabrachial subnucleus. However, this subnucleus also projected to all the other intralaminar thalamic nuclei, except for the central lateral thalamic nucleus, which received no parabrachial afferent inputs. The external lateral parabrachial subnucleus projected to the lateral parafascicular, reuniens, central medial, parvicellular part of the ventral posterior, and caudal ventromedial thalamic nuclei. Following CTb injections in the paraventricular thalamic nucleus, retrogradely labeled cells were found in the central lateral, dorsal lateral, and external lateral parabrachial subnuclei. The medial and ventral lateral parabrachial subnuclei projected to the oval paracentral, parafascicular, and rhomboid thalamic nuclei. Finally, the waist area of the parabrachial nucleus was densely labeled after CTb injections in the parvicellular part of the ventral posterior thalamic nucleus. Nociceptive, visceral, and gustatory signals may reach specific cortical and other forebrain sites via this parabrachial-thalamic pathway.

Adrenalectomy or metyrapone-pretreatment abolishes cerebral metabolic responses to the serotonin agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in the hippocampus

1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a serotonin type 2 (5-HT 2) agonist, elevates plasma corticosterone levels and reduces the cerebral metabolic rate for glucose (rCMRglc) in the hippocampus, a structure which possesses few 5-HT 2 receptors but a large number of steroid receptors. To explore the hypothetical interaction between 5-HT and steroid mechanisms in the hippocampus, we measured rCMRgic in intact, adrenalectomized and metyrapone-pretreated rats after saline or DOI administration. Metyrapone pretreatment alond had no significant effect on rCMRglc, but adrenalectomy produced widespread rCMRgic increases in the cortex, hippocampus and monoaminergic brainstem nuclei. In intact rats, DOI 10 mg/kg reduced rCMRgic in limbic areas and increased it in the interanteromedial and paracentral thalamic nuclei. Metyrapone pretreatment and adrenalectomy abolished rCMRgic responses to DOI in hippocampal areas and enhanced those in thalamic nuclei. These results indicate that brain responses to DOI are dependent upon the functional state of the hypothalamus-pituitary-adrenal cortex axis.

The distribution and cellular localization of the serotonin 1C receptor mRNA in the rodent brain examined by in situ hybridization histochemistry. Comparison with receptor binding distribution

The regional distribution and cellular localization of mRNA coding for the serotonin 1C receptor were investigated in tissue sections of mouse and rat brain by in situ hybridization histochemistry. Several 32P-labelled riboprobes derived from mouse genomic clones were used. The serotonin 1C receptor binding sites were visualized autoradiographically and quantified using [ 3H]mesulergine as ligand, in the presence of spiperone to block serotonin 1C receptors. Strong hybridization signal was observed in the choroid plexus of all brain ventricles. High levels of hybridization were also seen in the anterior olfactory nucleus, pyriform cortex, amygdala, some thalamic nuclei, especially the lateral habenula, the CA3 area of the hippocampal formation, the cingulate cortex, some components of the basal ganglia and associated areas, particularly the nucleus subthalamicus and the substantia nigra. The midbrain and brainstem showed moderate levels of hybridization. The distribution of the serotonin 1C receptor mRNA corresponded well to that of the serotonin 1C receptors. The highest levels of the serotonin 1C receptor binding were observed in the choroid plexus. In addition, significant levels of the serotonin 1C receptor binding were seen in the anterior olfactory nucleus, pyriform cortex, nucleus accumbens, ventral aspects of the striatum, paratenial and paracentral thalamic nuclei, amygdaloid body and substantia nigra pars reticulata. The cingulate and retrosplenial cortices as well as the caudal aspects of the hippocampus (CA3) were also labelled. Binding in brainstem and medulla was low and homogeneously distributed. No significant binding was seen in the habenular and subthalamic nuclei. Similar findings were obtained in rat brain. These results demonstrate that, in addition to their enrichment in the choroid plexus, the serotonin 1C receptor mRNA and binding sites are heterogeneously distributed in the rodent brain and thus could be involved in the regulation of many different brain functions. The combination of in situ hybridization histochemistry with receptor autoradiography opens the possibility of examining the regulation of the serotonin 1C receptor synthesis after pharmacological or physiological alterations.

The early involvement of subcortical structures during the development of a cortical seizure focus.

Cortical surface electrodes and bipolar depth electrodes were implanted stereotaxically in the ventral posterolateral and paracentral thalamic nuclei, amygdala, hippocampus, and putamen in adult cats to determine the progressive involvement of these structures in the generalization of an experimentally induced seizure disorder. Prior to (45-65 days) and following (50-70 days) subpial injection of 0.04 ml of aluminum hydroxide in the sensorimotor cortex, 30 min EEG records were obtained regularly in each animal. At the time of aluminum hydroxide injection, there was no persistent abnormal EEG activity resulting from electrode implantation. In all animals, intermittent slow waves and epileptiform activity appeared in subcortical or extrafocal structures prior to the development of epileptiform activity in the primary focus. These abnormalities were frequently associated with brief clinical seizures and were clearly independent of abnormal activity in the primary focus. Only later in the development of the seizure disorder was activity in the secondary foci observed to be dependent on frequent epileptiform activity in the primary focus. These results demonstrate that multiple, independent foci develop in subcortical structures before the occurrence of a well developed, fully "mature" cortical primary focus.

Extrageniculate projections to the visual cortex in the macaque monkey: an HRP study

Extrageniculate projections to the visual cortex were examined in the macaque monkeys by the horseradish peroxidase (HRP) method. Extrageniculate neurons sending fibers to the visual cortex were found in the lateral and inferior pulvinar nuclei, paracentral thalamic nucleus, claustrum, basal nucleus of Meynert, lateral part of the basal amygdaloid nucleus, lateral hypothalamus, locus coeruleus, and dorsomedial and midline regions of the pontine tegmentum.

Efferent tectal pathways of the opossum (Didelphis virginiana).

AbstractEfferent tectal pathways have been determined for the opossum, Didelphis virginiana, by employing the Nauta‐Gygax technique ('54) on animals with tectal lesions of varying sizes. The superior colliculus projected tectothalamic fascicles to the suprageniculate nucleus, the central nucleus of the medial geniculate body, the lateral posterior thalamus, the pretectal nucleus, the ventral lateral geniculate nucleus, the fields of Forel and zona incerta, the parafascicular complex, the paracentral thalamic nucleus and in some cases to restricted areas of the anterior thalamus. Degenerating fibers from superior collicular lesions showed profuse distribution to the deeper layers of the superior colliculus on both sides and to the midbrain tegmentum, but only minimally to the red nucleus and substantia nigra. Fibers of tectal origin did not distribute to the motor nuclei of the oculomotor or trochlear nerves. At pontine levels, efferent fascicles from the superior colliculus were present as an ipsilateral tectopontine and tectobulbar tract and as a crossed predorsal bundle. The tectopontine tract ended mostly within the lateral and ventral basal pontine nuclei, whereas the ipsilateral tectobulbar tract distributed to certain specific areas of the reticular formation throughout the pons and medulla, minimally to the most medial portion of the motor nucleus of the facial nerve and to the nucleus of the inferior olive. The predorsal tract contributed fascicles to certain nuclei of the pontine raphe, extensively to the medial reticular formation of the pons, to the central and ventral motor tegmental nuclei of the reticular formation within the pons and medulla, to the paraabducens region, minimally to cells within restricted portions of the motor nucleus of the facial nerve, to certail specific regions of the caudal medulla and to the cervical cord as far caudally as the fourth segment. The tectospinal fascicles were few but some ended related to the spinal accessory nucleus and the ventral medial nucleus of the ventral horn.Lesions of the inferior colliculus resulted in degenerating fibers which distributed rostrally to the rostral nucleus of the lateral lemniscus and parabrachial region, to the suprageniculate nucleus, the parabigeminal nucleus and to the central nucleus of the medial geniculate body. The inferior colliculus also contributed fibers to the ipsilateral tectopontine and tectobulbar tracts. The latter bundle was traced as far caudally as the medulla and may arise from cells of the superior colliculus which are situated dorsal to the nucleus of the inferior colliculus.