Bárbara Guimarães Salazar Coimbra - ICVS, University of Minho
Title: Impairments in laterodorsal tegmentum to VTA projections underlie glucocorticoid triggered reward deficits
Abstract:
Ventral tegmental area (VTA) activity is critical for motivated behaviours and reinforcement. Importantly, VTA activity is tightly modulated by afferents arising from the laterodorsal tegmentum (LDT). Disruption of this circuit can ultimately increase the risk for the development of neuropsychiatric disorders, including those associated with reward deficits, such as depression, anxiety, obsessive-compulsive disorder, obesity, addiction or antisocial behaviour. Additionally, the VTA region is particularly vulnerable to the effects of stress/glucocorticoids (GCs). Previous studies revealed that in utero exposure to glucocorticoids (iuGC) triggers prominent reward deficits later in life but nothing is known about the impact of this exposure in the LDT-VTA circuit.
Here, we show that iuGC animals have long-lasting changes in the expression of cholinergic markers in the LDT, and in vivo singe-cell electrophysiology revealed that LDT basal activity was decreased.
Interestingly, we observe a bidirectional effect in LDT-VTA inputs: upon LDT stimulation, iuGC animals present a decrease in the magnitude of excitation and an increase in the magnitude of inhibition in the VTA. While in control animals most of the inhibitory responses arise from putative GABAergic neurons, in iuGC group there is a shift in the type of cells presenting inhibitory responses, with a significant increase in the number of dopaminergic neurons.
In agreement with LDT-VTA dysfunction, we show that iuGC animals present motivational deficits that are rescued by selective optogenetic activation of this pathway. Importantly, we also show that LDTVTA optogenetic stimulation is reinforcing, and that iuGC animals are more susceptible to the reinforcing properties of LDT-VTA stimulation.
Title: Impairments in laterodorsal tegmentum to VTA projections underlie glucocorticoid triggered reward deficits
Abstract:
Ventral tegmental area (VTA) activity is critical for motivated behaviours and reinforcement. Importantly, VTA activity is tightly modulated by afferents arising from the laterodorsal tegmentum (LDT). Disruption of this circuit can ultimately increase the risk for the development of neuropsychiatric disorders, including those associated with reward deficits, such as depression, anxiety, obsessive-compulsive disorder, obesity, addiction or antisocial behaviour. Additionally, the VTA region is particularly vulnerable to the effects of stress/glucocorticoids (GCs). Previous studies revealed that in utero exposure to glucocorticoids (iuGC) triggers prominent reward deficits later in life but nothing is known about the impact of this exposure in the LDT-VTA circuit.
Here, we show that iuGC animals have long-lasting changes in the expression of cholinergic markers in the LDT, and in vivo singe-cell electrophysiology revealed that LDT basal activity was decreased.
Interestingly, we observe a bidirectional effect in LDT-VTA inputs: upon LDT stimulation, iuGC animals present a decrease in the magnitude of excitation and an increase in the magnitude of inhibition in the VTA. While in control animals most of the inhibitory responses arise from putative GABAergic neurons, in iuGC group there is a shift in the type of cells presenting inhibitory responses, with a significant increase in the number of dopaminergic neurons.
In agreement with LDT-VTA dysfunction, we show that iuGC animals present motivational deficits that are rescued by selective optogenetic activation of this pathway. Importantly, we also show that LDTVTA optogenetic stimulation is reinforcing, and that iuGC animals are more susceptible to the reinforcing properties of LDT-VTA stimulation.