Abstract
The motor thalamus (MTh) plays a crucial role in the basal ganglia (BG)-cortical loop in motor information codification. Despite this, there is limited evidence of MTh functionality in normal and Parkinsonian conditions. To shed light on the functional properties of the MTh, we examined the effects of acute and chronic dopamine (DA) depletion on the neuronal firing of MTh neurons, cortical/MTh interplay and MTh extracellular concentrations of glutamate (GLU) and gamma-aminobutyric acid (GABA) in two states of DA depletion: acute depletion induced by the tetrodotoxin (TTX) and chronic denervation obtained by 6-hydroxydopamine (6-OHDA), both infused into the medial forebrain bundle (MFB) in anesthetized rats. The acute TTX DA depletion caused a clear-cut reduction in MTh neuronal activity without changes in burst content, whereas the chronic 6-OHDA depletion did not modify the firing rate but increased the burst firing. The phase correlation analysis underscored that the 6-OHDA chronic DA depletion affected the MTh-cortical activity coupling compared to the acute TTX-induced DA depletion state. The TTX acute DA depletion caused a clear-cut increase of the MTh GABA concentration and no change of GLU levels. On the other hand, the 6-OHDA-induced chronic DA depletion led to a significant reduction of local GABA and an increase of GLU levels in the MTh. These data show that MTh is affected by DA depletion and support the hypothesis that a rebalancing of MTh in the chronic condition counterbalances the profound alteration arising after acute DA depletion state.
Highlights
The motor thalamus (MTh) plays a pivotal role in motor information processing in both physiological and pathological conditions, being directly connected to both the basal ganglia (BG) and the cortex [1]
Another source of gamma-aminobutyric acid (GABA) in the MTh comes from the nucleus reticular thalami (NRT) [5], a thin layer of GABAergic cells adjacent to the relay nuclei of the dorsal thalamus, that we have shown to be able to modulate the oscillatory activity of MTh in dopamine (DA)-depleted animals [6]
This agrees with clinical evidence showing that clinical effective sub-thalamic nucleus (STN) deep brain stimulation (DBS) or even levodopa (L-DOPA) in Parkinson’s disease (PD) patients reversibly reduced the extracellular MTh GABA [20,21]
Summary
The motor thalamus (MTh) plays a pivotal role in motor information processing in both physiological and pathological conditions, being directly connected to both the basal ganglia (BG) and the cortex [1]. A decrease of GABA has been observed in the MTh of 6-OHDA-lesioned rats [22] and certain regions of the thalamus of post-mortem PD brains [23] These discrepancies cannot be only due to the difference in BG circuitry in rats compared to humans. Our main hypothesis was that the MTh is altered differently during rapid changes of DA levels compared to chronic depleted states This might account for the controversial findings on MTh. Since the BG activity changes in relation to the cortical pattern [28,29], all the recordings were performed during stable cortical slow-wave activity (SWA) induced by urethane anesthesia. We measured the extracellular levels of GABA and GLU by microdialysis in the same experimental conditions
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