Estudio de las proyecciones del pálido ventral a los grupos colinérgicos del tegmento mesopontino y a otras estructuras troncoencefálicas mediante trazado axonal anterógrado en la rata

Resumen

Projections from the ventral pallidum to the cholinergic nuclei of the mesopontine tegmentum and other troncoencephalic structures by anterograde axonal tracing in the rat Doctoral Dissertation Eva Pérez Lorenzo CIMA, University of Navarra, Pamplona (Spain) 2009 The ability of a weak stimulus to block the motor response to a closely following intense stimulus is called prepulse inhibition (PPI). PPI reflects a physiological inhibitory mechanism of sensorimotor gating, that prevents interferences due to overstimulation and thus favors attention and thought cohesion. PPI is disrupted in some neuropsychiatric disorders, such as schizophrenia, as well as in some neurodegenerative diseases, like Parkinson¿s disease. The ventral pallidum (VP) is known to play a role in the modulation of the PPI, putatively through downstream projections to the cholinergic neurons of the tegmental pedunculopontine (PPTg) and tegmental laterodorsal (LDTg) nuclei. However, anatomical studies have not shown this projection clearly. The aim of the present work was to analyse the downstream projections from the neurochemically delineated VP to the cholinergic neurons of the mesopontine tegmentum and other brainstem structures. Our results have clearly shown the presence of pallidal fibers within the cholinergic territory of PPTg and LDTg, thus providing the anatomical substrate for the functional modulation of these cholinergic neurons from VP. Putative synaptic contacts were not detected between the terminal fibers and the cholinergic neurons. This suggests that VP is not acting directly on the cholinergic neurons, but rather via interneurons. LDTg receives significantly more projections than PPTg, thus emerging as the preferential target of the VP projections. We have also studied these projections in relation to the two compartments of VP, being the ventrolateral compartment (VPl) part of the motor subcircuit of the ventral striatal pallidal pathway, and the ventromedial compartment (VPm) part of the limbic one. In relation to the two compartments, the pallidal projections to LDTg arise essentially from VPm while ones reaching PPTg originate mainly from VPl. These results indicate that the cholinergic complex Ch5-Ch6 is anatomically and functionally segregated into a motor and a limbic component, represented by PPTg and LDTg, respectively. In relation to other brainstem targets of the VP, the substantia nigra compacta (SNc) and the ventral tegmental area (VTA) are differentially innervated by the two components of VP, so that SNc receives a dense projection from VPl and VTA from VPm. Thus is consistent with previous anatomical and physiological studies reporting that the substantia nigra compacta participates in motor circuits, whereas the ventral tegmental area is implicated in motivational and reward circuits. All forebrain-projecting serotonergic nuclei receive moderate to dense projections from VP, being the median raphe nucleus the most densely innervated. Since these nuclei are affected in some neurodegenerative diseases, these pallidal projections from ventral circuits of the basal ganglia may in part provide an anatomical substrate for the frequent associations of mood disorders with Parkinson¿s disease. The retrorubral field and the deep mesencephalic nucleus also receive a strong projection from VP. These two nuclei are implicated in orofacial movements; therefore VP may be modulating these movements. Finally, the serotonergic nuclei are known to play a role in REM sleep. The VP projections to these nuclei together with a sparse ventral pallidal projection to some structures related with oculomotor activity, may represent the anatomical pathway for the motivational control of REM sleep and/or eye movements.