The reticular thalamic nucleus: revealing a novel phenotype of neurons and describing changes in a rat model of Parkinson’s disease.
The reticular thalamic nucleus (RTN) is a thin band of neurons that lies between the cortex and the rest of the thalamus. Most of the inputs to the nucleus are from collateral axons of thalamocortical and corticothalamic projections. The basal ganglia, basal forebrain and brainstem also have important connections to the RTN. The RTN has previously been characterized as an exclusively GABAergic nucleus that causes inhibition of thalamic relay neurons and modulates motor messages through thalamocortical projections. However, a small number of studies suggest that the RTN is not exclusively GABAergic, but did not define the phenotype of non-GABAergic neurons. The RTN is divided into sectors that represent all sensory modalities, and the limbic and motor systems. Each sector is closely connected to the functionally related thalamic regions. For example, the motor sector of the rostral RTN (rRTN) projects to the motor thalamus and receives inputs back from the motor thalamus, as well as from the motor cortex and the basal ganglia. This motor sector is active during movements and its activity changes with movements to coordinate the motor signals that are passed to the motor cortex. Despite its involvement in movement, the rRTN is not usually considered in movement related disorders such as Parkinson’s disease (PD). PD is a neurodegenerative disorder that is characterized by substantial loss of dopamine neurons in the substantia nigra pars compacta and the ventral tegmental area. Loss of these midbrain dopaminergic neurons underlies the hallmark motor symptoms in PD patients such as bradykinesia, akinesia, resting tremor and rigidity. To advance the understanding of the RTN and its role in PD, this study aimed to characterize the phenotype of neurons within the rRTN of adult rats and investigate the effect of 6 hydroxydopamine (6 OHDA) induced lesions of midbrain dopaminergic neurons on the number and morphology of neurons in the rRTN. Chromogenic and fluorescent immunohistochemistry for the GABAergic marker GAD67 and the glutamatergic marker CaMKIIα confirmed that the majority of neurons were indeed GABAergic and a small novel population of neurons exist in the rRTN that are CaMKIIα positive. Furthermore, a lentiviral vector was injected into the rRTN that selectively labelled neurons expressing CaMKIIα with the fluorophore mCherry. Detection of mCherry in transduced neurons and GAD67 with fluorescent immunohistochemistry confirmed that there are two distinct populations of neurons in the rRTN. Chronic dopamine lesions were induced in the left hemisphere of the brain by the injection of the neurotoxin 6 OHDA. Stereological investigations into the number and morphology of neurons in the rRTN revealed that 6-OHDA lesion induced a 20% increase in the number of GABAergic neurons and also produced a 20% decrease in the size of GABAergic neurons in the rRTN. These changes were not seen in glutamatergic neurons. These data indicate that the rRTN is not exclusively GABAergic, as once thought, and although small, this glutamatergic population may play an important role in RTN function. Furthermore, dopamine depletion causes a number of changes in the rRTN, therefore, the rRTN may be a novel target in the treatment of PD.
Advisor: Parr-Brownlie, Louise
Degree Name: Master of Science
Degree Discipline: Anatomy
Publisher: University of Otago
Keywords: reticular thalamic nucleus; 6-ohda; Parkinson's disease
Research Type: Thesis