Efferent projections of the thalamic intralaminar nuclei in the cat.

Efferent projections of the central lateral (CL), paracentral (PC) and central medial (CE) intralaminar nuclei (ILN) to cortical and subcortical sites were studied in the cat. The combined methods of electrophysiologically guided cortical injections of tritiated leucine and stereotaxic injections of horseradish peroxidase (HRP) into the CL and PC nuclei were utilized. Additionally, fluorescent double-labeling techniques demonstrated patterns of intralaminar axon collateralization. We found that the ILN project ipsilaterally to all visual cortical areas except area 17. Projections to visual cortex are not arranged topographically or retinotopically. The ILN also project to the frontal eye fields (areas 6 and 8), anterior cingulate gyrus, suprasylvian fringe of the auditory cortex, insular cortex, parietal areas 5 and 7, caudate nucleus and claustrum. We noted especially heavy projections to the frontal eye fields and parietal areas 5 and 7. Fibers from the ILN terminate in cortical layers I and VI, and at the layer III-IV border. The demonstration of collateralization of ILN axons to two separate cortical areas implies that the same neuronal message may pass from the ILN to multiple cortical areas. It is concluded that the ILN may mediate a general cortical activation and may play a role in attention to visual, auditory and somatosensory (especially nociceptive) stimuli.

Afferent connections of the thalamic intralaminar nuclei in the cat.

Afferents to the central lateral (CL), paracentral (PC) and central medial (CE) intralaminar nuclei (ILN) from cortical and subcortical sites were studied in the cat. We utilized stereotaxically guided injections of HRP into the CL and PC nuclei and tritiated leucine injections into various visual, parietal and limbic areas of cortex to demonstrate these connections. In studying the relatively weak visual cortical projections to the ILN, we demonstrated projections from areas 19, 20a, 21a, 21b, AMLS, PMLS and PLLS. However, our HRP injections into the ILN often revealed only a few labeled cells in any of the above areas; therefore conclusions regarding the absence of projections to ILN from remaining visual cortical areas should be made cautiously. The ILN receive heavier projections from the frontal eye fields, cingulate cortex, splenial cortex, insular cortex, somatosensory areas SI and SII, auditory areas SF, AII, and Ep, and parietal areas 5 and 7. The most robust projections appear to be from from frontal eye fields, cingulate and parietal areas. No topography was apparent in the projections to the ILN. All cortical projections originate ipsilaterally from layers V and VI. Heavy subcortical projections to the ILN originate in the pretectum, superior colliculus, reticular formation, and periaqueductal grey. Fewer afferents arise from several other brainstem and thalamic nuclei.

Cholecystokinin antagonists selectively potentiate analgesia induced by endogenous opiates.

We have recently observed that exogenous sulfated cholecystokinin octapeptide (CCK) can antagonize various forms of opiate analgesia and that the CCK receptor blocker proglumide potentiates morphine analgesia. These observations, plus the similarity in the distribution of CCK and opiate systems, suggest that endogenous CCK may act as a physiological opiate antagonist. We have extended these initial studies by examining the effect of CCK antagonists on opiate analgesia produced by release of endogenous opiates (front paw footshock induced analgesia) and by intrathecal administration of D-Ala-methionine enkephalinamide, a stable analogue of an endogenous opiate. Additionally, the specificity of proglumide's effect was examined by testing the effect of this drug on various forms of non-opiate analgesia. This series of experiments demonstrate that CCK antagonists can markedly potentiate analgesia induced by endogenous opiates and provide strong support for the hypothesis that endogenous CCK systems can oppose the analgesic effects of opiates. Potentiation of analgesia by CCK receptor blockers appears to be selective for opiate systems since proglumide typically attenuated or had no effect on various forms of non-opiate analgesia. These data suggest that CCK blockers may be clinically useful for enhancing the analgesic effects of procedures such as acupuncture, which may be mediated by release of endogenous opiates.

The projections of single thalamic neurons onto multiple visual cortical areas in the cat.

Fluorescent dyes Fast Blue and Nuclear Yellow injected into pairs of visual cortical and parietal 'association' cortical areas in the cat revealed the presence of retrogradely double-labeled cells in the intralaminar nuclei and lateral posterior-pulvinar complex of the thalamus. These results demonstrate the projection of individual thalamic neurons onto multiple cortical areas.