The projections from the brainstem to the midline and intralaminar thalamic nuclei were examined in the rat. Stereotaxic injections of the retrograde tracer cholera toxin beta -subunit (CTb) were made in each of the intralaminar nuclei of the dorsal thalamus: the lateral parafascicular, medial parafascicular, central lateral, paracentral, oval paracentral, and central medial nuclei; in the midline thalamic nuclei-the paraventricular, intermediodorsal, mediodorsal, paratenial, rhomboid, reuniens, and submedius nuclei; and, in the anteroventral, parvicellular part of the ventral posterior, and caudal ventral medial nuclei. The retrograde cell body labeling pattern within the brainstem nuclei was then analyzed. Nearly every thalamic site received a projection from the deep mesencephalic reticular, pedunculopontine tegmental, dorsal raphe, median raphe, laterodorsal tegmental, and locus coeruleus nuclei. Most intralaminar thalamic sites were also innervated by unique combinations of medullary and pontine reticular formation nuclei such as the subnucleus reticularis dorsalis, gigantocellular, dorsal paragigantocellular, lateral, parvicellular, caudal pontine, ventral pontine, and oral pontine reticular nuclei; the dorsomedial tegmental, subpeduncular tegmental, and ventral tegmental areas; and, the central tegmental field. In addition, most intralaminar injections resulted in retrograde cell body labeling in the substantia nigra, nucleus Darkschewitsch, interstitial nucleus of Cajal, and cuneiform nucleus. Details concerning the pathways from the spinal trigeminal, nucleus tractus solitarius, raphe magnus, raphe pallidus, and the rostral and caudal linear raphe nuclei to subsets of midline and intralaminar thalamic sites are discussed in the text. The discussion focuses on brainstem-thalamic pathways that are likely involved in arousal, somatosensory, and visceral functions.

The physiological characteristics of antidromically identified lamina I spinothalamic (STT) neurons in the lumbosacral spinal cord were examined using quantitative thermal and mechanical stimuli in barbiturate-anesthetized cats. Cells belonging to the three main recognized classes were included based on categorization with natural cutaneous stimulation of the hindpaw: nociceptive-specific (NS), polymodal nociceptive (HPC), or thermoreceptive-specific (COOL) cells. The mean central conduction latencies of these classes differed significantly; NS = 130.8 +/- 55.5 (SD) ms (n = 100), HPC = 72.1 +/- 28.0 ms (n = 128), and COOL = 58.6 +/- 25.3 ms (n = 136), which correspond to conduction velocities of 2.5, 4.6, and 5.6 m/s. Based on recordings made prior to any noxious stimulation, the mean spontaneous discharge rates of these classes also differed: NS = 0.5 +/- 0.7 imp/s (n = 47), HPC = 0.9 +/- 0.7 imp/s (n = 59), and COOL = 3.3 +/- 2.6 imp/s (n = 107). Standard, quantitative, thermal stimulus sequences applied with a Peltier thermode were used to characterize the stimulus-response functions of 76 COOL cells, 47 HPC cells, and 37 NS cells. The COOL cells showed a very linear output from 34 degrees C down to approximately 15 degrees C and a maintained plateau thereafter. The HPC cells showed a fairly linear but accelerating response to cold below a median threshold of approximately 24 degrees C and down to 9 degrees C (measured at the skin-thermode interface with a thermode temperature of 2 degrees C). The HPC cells and the NS cells both showed rapidly increasing, sigmoidal response functions to noxious heat with a fairly linear response between 45 and 53 degrees C, but they had significantly different thresholds; half of the HPC cells were activated at ~45.5 degrees C and half of the NS cells at approximately 43 degrees C. The 20 HPC lamina I STT cells and 10 NS cells tested with quantitative pinch stimuli showed fairly linear responses above a threshold of approximately 130 g/mm(2) for HPC cells and a threshold of approximately 100 g/mm(2) for NS cells. All of these response functions compare well (across species) with the available data on the characteristics of thermoreceptive and nociceptive primary afferent fibers and the appropriate psychophysics in humans. Together these results support the concept that these classes of lamina I STT cells provide discrete sensory channels for the sensations of temperature and pain.

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.

The periaqueductal gray matter (PAG) projections to the intralaminar and midline thalamic nuclei were examined in rats. Phaseolus vulgaris-leucoagglutinin (PHA-L) was injected in discrete regions of the PAG, and axonal labeling was examined in the thalamus. PHA-L was also placed into the dorsal raphe nuclei or nucleus of Darkschewitsch and interstitial nucleus of Cajal as controls. In a separate group of rats, the retrograde tracer cholera toxin beta-subunit (CTb) was injected into one of the intralaminar thalamic nuclei-lateral parafascicular, medial parafascicular, central lateral (CL), paracentral (PC), or central medial nucleus-or one of the midline thalamic nuclei-paraventricular (PVT), intermediodorsal (IMD), mediodorsal, paratenial, rhomboid (Rh), reuniens (Re), or caudal ventral medial (VMc) nucleus. The distribution of CTb labeled neurons in the PAG was then mapped. All PAG regions (the four columns of the caudal two-thirds of the PAG plus rostral PAG) and the precommissural nucleus projected to the rostral PVT, IMD, and CL. The ventrolateral, lateral, and rostral PAG provided additional inputs to most of the other intralaminar and midline thalamic nuclei. PAG inputs to the VMc originated from the rostral and ventrolateral PAG areas. In addition, the lateral and rostral PAG projected to the zona incerta. No evidence was found for a PAG input to the ventroposterior lateral parvicellular, ventroposterior medial parvicellular, caudal PC, oval paracentral, and reticular thalamic nuclei. PAG --> thalamic circuits may modulate autonomic-, nociceptive-, and behavior-related forebrain circuits associated with defense and emotional responses.