Speakers - NWC 2024

Abstract

Recent studies (Puelles et al. 2023) on the developmental genoarchitecture and connections of mouse hypothalamic entopeduncular and pallidal nuclei concluded that, in particular, the ventral entopeduncular nucleus is not homologous to the internal globus pallidus of primates, as is usually assumed in the literature since 1930. Distinct telencephalic external and internal globus pallidus grisea do exist in rodents, strictly comparable in position and cellular and molecular properties to pallidal nuclei in primates (only the external pallidus was thought to be present since the internal pallidus was supposed to be in the hypothalamus). Entopeduncular nuclei have not been reported before in primates (assuming these cells had migrated into pallidal positions); since the postulated hypothalamo-telencephalic migrations do not exist, the corresponding primate entopeduncular hypothalamic formations probably are cryptic or were misidentified as part of the internal globus pallidus (there is a sizeable enlargement of the cerebral peduncle in the hypothalamus of primates. The conclusion of our genoarchitectonic developmental studies, jointly with corroborating public connectivity data extracted from the Allen Mouse Brain Connectivity Map, is that all mammals must have both external and internal globus pallidus centers in the telencephalic subpallium, as well as a parallel set of entopeduncular nuclei in the hypothalamus. All these nuclei are involved in the circuitry whose functionality is affected in Parkinson’s disease due to failure of their differential striatal inhibitory input after degeneration of nigrostriatal dopaminergic neurons. The mouse GABAergic ventral entopeduncular nucleus has been revealed to project to the motor thalamus, exactly like the mouse internal globus pallidus, indicating that the crucial inhibitory pallido-thalamic connections are duplicated in mammals, implicitly also in primates and humans. This comparative genoarchitectonic result introduces a subtle change in the Parkinsonian circuitry, which is of clinical interest.