Nigrostriatal collaterals to thalamus degenerate in parkinsonian animal models

Abstract

Movement, cognition, emotion, and positive reinforcement are influenced by mesostriatal, mesocortical, and mesolimbic dopamine systems. We describe a fourth major pathway originating from mesencephalic dopamine neurons: a mesothalamic system. The dopamine transporter, specific to dopamine containing axons, was histochemically visualized in thalamic motor and limbic-related nuclei and regions that modulate behavioral state as opposed to sensory nuclei in rats, nonhuman primates, and humans. Anatomical tracing established this innervation's origin via axon collaterals from the mesostriatal pathway. These findings implicate the thalamus as a novel site for disease specific alterations in dopamine neurotransmission, such as exist with nigral degeneration attending Parkinson's disease. This was confirmed in hemiparkinsonian animals where reduction of thalamic dopamine innervation occurred coincident with signs of active axonal degeneration. Individual mesencephalic dopamine neurons therefore have the potential to modulate normal and pathologic behavior not only through traditional nigrostriatal pathways but also by way of axon collaterals that innervate the thalamus.

Identification of Wake-Active Dopaminergic Neurons in the Ventral Periaqueductal Gray Matter

“…The vPAG dopaminergic projections to the prefrontal cortex Yoshida et al, 1989) and the midline and intralaminar thalamus (Takada et al, 1990;Freeman et al, 2001) have been identified previously. The dopamine transporter (Freeman et al, 2001) and D 1 and D 2 dopamine receptors (Huang et al, 1992;Lewis and O'Donnell, 2000) are present in both the thalamus and the cerebral cortex, suggesting that dopamine can directly influence thalamocortical activity.…”

“…Despite this evidence, the specific population of dopaminergic neurons responsible for arousal is not known. VTA neurons that project to the prefrontal cortex and striatum (Steinfels et al, 1983;Freeman et al, 2001) are often assumed to play this role; however, the firing of VTA neurons or SN neurons that project to the striatum does not correlate with overall levels of behavioral wakefulness in rats (Miller et al, 1983). Furthermore, neurotoxic lesions of the VTA do not decrease behavioral wakefulness (Lai et al, 1999).…”

Modelagem neurocomputacional do circuito tálamo-cortical: implicações para compreensão do transtorno de défi cit de atenção e hiperatividade

“…Como a dopamina nigral possui efeito inibitório no NRT 6,7 , o seu aumento gera uma diminuição na ativação dos neurônios desta região. No contexto do modelo, isso faz com que a área talâmica T y sofra menos inibição oriunda do NRT.…”

“…A formação do foco atencional passa pelo controle do circuito tála-mo-cortical, uma vez que o tálamo seleciona os estí-mulos externos a serem processados pelo córtex 4,5 . Experimentos histoquímicos realizados por Freeman et al 6 , tanto em humanos como em macacos, mostraram que a SN projeta, através da via mesotalâmica, neurô-nios dopaminérgicos em direção a núcleos talâmicos -em particular o núcleo reticular talâmico (NRT). Com isso, a SN possivelmente afeta diretamente a atividade do circuito tálamo-cortical e, portanto, modula a maneira pela qual o foco de atenção é consolidado.…”

“…Além disso, experimentos realizados por Florán et al 7 indicaram que receptores dopaminérgicos D4 inibem neurônios do NRT, em presença de cálcio e potássio. Baseados nos experimentos de Freeman et al 6 e Florán et al 7 , propomos um modelo neurocomputacional que fornece uma plausível explicação de como a projeção dopaminérgica oriunda da SN afeta o funcionamento do circuito tálamo-cortical.…”