scholarly journals Ventral tegmental area glutamate neurons mediate the nonassociative consequences of traumatic stress

2021 ◽  
Author(s):  
Dillon J McGovern ◽  
Koy L Ecton ◽  
David T Huynh ◽  
Andrew R Rau ◽  
Shane T Hentges ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Neuronal Activity ◽  
Neuron Activity ◽  
Social Avoidance ◽  
Ventral Tegmental ◽  
Behavioral Sequelae ◽  
Physically Identical ◽  
Neuron Function ◽  
Stressor Controllability ◽  
The Impact

Exposure to trauma is a risk factor for the development of a number of mood disorders, and may enhance vulnerability to future adverse life events. Recent data implicate ventral tegmental area (VTA) glutamate neuronal activity as functionally important for signaling aversive or threating stimuli. However, it is unknown whether VTA glutamate neurons regulate transsituational outcomes that result from stress and whether these neurons are sensitive to stressor controllability. This work established an operant mouse paradigm to examine the impact of stressor controllability on VTA glutamate neuron function and stressor outcome. Uncontrollable (inescapable) stress, but not physically identical controllable (escapable) stress, produced social avoidance in male mice. Cell-type-specific calcium recordings showed that both controllable and uncontrollable stressors increased VTA glutamate neuronal activity. Chemogenetic reduction of VTA glutamate neuron activity prevented the behavioral sequelae of uncontrollable stress. Our results provide causal evidence that mice can be used to model stressor controllability and that VTA glutamate neurons may contribute to transsituational stressor outcomes, such as social avoidance and exaggerated fear that are observed within trauma-related disorders.

scholarly journals Impairments in laterodorsal tegmentum to VTA projections underlie glucocorticoid-triggered reward deficits

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Bárbara Coimbra ◽  
Carina Soares-Cunha ◽  
Sónia Borges ◽  
Nivaldo AP Vasconcelos ◽  
Nuno Sousa ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Neuronal Activity ◽  
In Utero ◽  
In Utero Exposure ◽  
Optogenetic Stimulation ◽  
Ventral Tegmental ◽  
Laterodorsal Tegmentum ◽  
The Impact ◽  
Cholinergic Markers

Ventral tegmental area (VTA) activity is critical for reward/reinforcement and is tightly modulated by the laterodorsal tegmentum (LDT). In utero exposure to glucocorticoids (iuGC) triggers prominent motivation deficits but nothing is known about the impact of this exposure in the LDT-VTA circuit. We show that iuGC-rats have long-lasting changes in cholinergic markers in the LDT, together with a decrease in LDT basal neuronal activity. Interestingly, upon LDT stimulation, iuGC animals present a decrease in the magnitude of excitation and an increase in VTA inhibition, as a result of a shift in the type of cells that respond to the stimulus. 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 LDT-VTA optogenetic stimulation is reinforcing, and that iuGC animals are more susceptible to the reinforcing properties of LDT-VTA stimulation.

scholarly journals Control of the Nigrostriatal Dopamine Neuron Activity and Motor Function by the Tail of the Ventral Tegmental Area

2014 ◽  
Vol 39 (12) ◽  
pp. 2788-2798 ◽  
Author(s):  
Romain Bourdy ◽  
María-José Sánchez-Catalán ◽  
Jennifer Kaufling ◽  
Judith J Balcita-Pedicino ◽  
Marie-José Freund-Mercier ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Motor Function ◽  
Dopamine Neuron ◽  
Neuron Activity ◽  
Nigrostriatal Dopamine ◽  
Ventral Tegmental

scholarly journals Adiponectin modulates ventral tegmental area dopamine neuron activity and anxiety-related behavior through AdipoR1

2018 ◽  
Vol 24 (1) ◽  
pp. 126-144 ◽  
Author(s):  
Fengjiao Sun ◽  
Yun Lei ◽  
Jingjing You ◽  
Chen Li ◽  
Linshan Sun ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Dopamine Neuron ◽  
Neuron Activity ◽  
Ventral Tegmental

scholarly journals Neurotensin inhibits both dopamine- and GABA-mediated inhibition of ventral tegmental area dopamine neurons

2015 ◽  
Vol 114 (3) ◽  
pp. 1734-1745 ◽  
Author(s):  
Katherine Stuhrman ◽  
Aaron G. Roseberry
Keyword(s):  
Ventral Tegmental Area ◽  
Calcium Release ◽  
Transient Receptor Potential ◽  
Brain Slices ◽  
Receptor Activation ◽  
Dopamine Neuron ◽  
Dopamine Neurons ◽  
Neuron Activity ◽  
Inward Current ◽  
Ventral Tegmental

Dopamine is an essential neurotransmitter that plays an important role in a number of different physiological processes and disorders. There is substantial evidence that the neuropeptide neurotensin interacts with the mesolimbic dopamine system and can regulate dopamine neuron activity. In these studies we have used whole cell patch-clamp electrophysiology in brain slices from mice to examine how neurotensin regulates dopamine neuron activity by examining the effect of neurotensin on the inhibitory postsynaptic current generated by somatodendritic dopamine release (D2R IPSC) in ventral tegmental area (VTA) dopamine neurons. Neurotensin inhibited the D2R IPSC and activated an inward current in VTA dopamine neurons that appeared to be at least partially mediated by activation of a transient receptor potential C-type channel. Neither the inward current nor the inhibition of the D2R IPSC was affected by blocking PKC or calcium release from intracellular stores, and the inhibition of the D2R IPSC was greater with neurotensin compared with activation of other Gq-coupled receptors. Interestingly, the effects of neurotensin were not specific to D2R signaling as neurotensin also inhibited GABAB inhibitory postsynaptic currents in VTA dopamine neurons. Finally, the effects of neurotensin were significantly larger when intracellular Ca2+ was strongly buffered, suggesting that reduced intracellular calcium facilitates these effects. Overall these results suggest that neurotensin may inhibit the D2R and GABAB IPSCs downstream of receptor activation, potentially through regulation of G protein-coupled inwardly rectifying potassium channels. These studies provide an important advance in our understanding of dopamine neuron activity and how it is controlled by neurotensin.

scholarly journals nNOS-expressing neurons in the ventral tegmental area and substantia nigra pars compacta

2018 ◽  
Author(s):  
Eleanor J Paul ◽  
Eliza Kalk ◽  
Kyoko Tossell ◽  
Elaine E. Irvine ◽  
Dominic J. Withers ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Brain Regions ◽  
Substantia Nigra Pars Compacta ◽  
Neuron Activity ◽  
Potential Candidate ◽  
Gaba Neurons ◽  
Local Interneurons ◽  
Ventral Tegmental ◽  
Oxide Synthase

AbstractGABA neurons in the ventral tegmental area (VTA) and substantia nigra pars compact (SNc) play key roles in reward and aversion through their local inhibitory control of dopamine neuron activity and through long-range projections to several target regions including the nucleus accumbens. It is not clear if some of these GABA neurons are dedicated local interneurons or if they all collateralize and send projections externally as well as making local synaptic connections. Testing between these possibilities has been challenging in the absence of interneuron-specific molecular markers. We hypothesised that one potential candidate might be neuronal nitric oxide synthase (nNOS), a common interneuronal marker in other brain regions. To test this, we used a combination of immunolabelling (including antibodies for nNOS that we validated in tissue from nNOS-deficient mice) and cell-type-specific virus-based anterograde tracing in mice. We show that nNOS-expressing neurons in the parabrachial pigmented (PBP) part of the VTA and the SNc are GABAergic local interneurons, whereas nNOS-expressing neurons in the Rostral Linear Nucleus (RLi) are mostly glutamatergic and project to a number of regions, including the lateral hypothalamus, the ventral pallidum, and the median raphe nucleus. Taken together, these findings indicate that nNOS is expressed by neurochemically- and anatomically-distinct neuronal sub-groups in a sub-region-specific manner in the VTA and SNc.

scholarly journals Distracting stimuli evoke ventral tegmental area responses in rats during ongoing saccharin consumption

2020 ◽  
Author(s):  
Kate Z Peters ◽  
Andrew M J Young ◽  
James E McCutcheon
Keyword(s):  
Ventral Tegmental Area ◽  
Neuronal Activity ◽  
Neural Responses ◽  
Internal States ◽  
Licking Behaviour ◽  
Psychiatric Conditions ◽  
Ventral Tegmental ◽  
Adaptive Behaviours ◽  
External Stimuli

AbstractDisruptions in attention, salience and increased distractibility are implicated in multiple psychiatric conditions. The ventral tegmental area (VTA) is a potential site for converging information about external stimuli and internal states to be integrated and guide adaptive behaviours. Given the dual role of dopamine signals in both driving ongoing behaviours (e.g. feeding) and monitoring salient environmental stimuli, understanding the interaction between these functions is crucial. Here we investigate VTA neuronal activity during distraction from ongoing feeding. We developed a task to assess distraction exploiting self-paced licking in rats. Rats trained to lick for saccharin were given a distraction test, in which three consecutive licks within 1 second triggered a random distractor (e.g. light and tone stimulus). On each trial they were quantified as distracted or not based on the length of their pauses in licking behaviour. We expressed GCaMP6s in VTA neurons and used fibre photometry to record calcium fluctuations during this task as a proxy for neuronal activity. Distractor stimuli caused rats to interrupt their consumption of saccharin, a behavioural effect which quickly habituated with repeat testing. VTA neural activity showed consistent increases to distractor presentations and, furthermore, these responses were greater on distracted trials compared to non-distracted trials. Interestingly, neural responses show a slower habituation than behaviour with consistent VTA responses seen to distractors even after they are no longer distracting. These data highlight the complex role of the VTA in maintaining ongoing appetitive and consummatory behaviours while also monitoring the environment for salient stimuli.

scholarly journals HCN2 channels in the ventral tegmental area regulate behavioral responses to chronic stress

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Peng Zhong ◽  
Casey R Vickstrom ◽  
Xiaojie Liu ◽  
Ying Hu ◽  
Laikang Yu ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Chronic Stress ◽  
Ex Vivo ◽  
Critical Role ◽  
Dopamine Neuron ◽  
Dopamine Neurons ◽  
Neuron Activity ◽  
Hcn Channels ◽  
Neuron Firing ◽  
Ventral Tegmental

Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by voltage-gated ion channels, in particular hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Following CMS, HCN-mediated currents were decreased in nucleus accumbens-projecting VTA dopamine neurons. Furthermore, shRNA-mediated HCN2 knockdown in the VTA was sufficient to recapitulate CMS-induced depressive- and anxiety-like behavior in stress-naïve mice, whereas VTA HCN2 overexpression largely prevented CMS-induced behavioral deficits. Together, these results reveal a critical role for HCN2 in regulating VTA dopamine neuronal activity and depressive-related behaviors.

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