Dopamine release and negative valence gated by inhibitory neurons in the laterodorsal tegmental nucleus

Du, Yong-lan; Zhou, Siyao; Ma, Chenyan; Chen, Hui; Du, Aifang; Deng, Guide; Liu, Yige; Tose, Amanda J.; Sun, Lei; Liu, Yi-Jun; Wu, Haixiao; Lou, Huifang; Yu, Yan-Qin; Zhao, Ting; Lammel, Stephan; Duan, Shumin; Yang, Huohai

doi:10.1016/j.neuron.2023.06.021

Cited by 8 publications

(3 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with this powerful effect, GABAergic inhibition is critical for dopamine neurons' responses to behaviorally relevant events including aversive stimuli ( Jhou et al, 2009 ; Li et al, 2019 ; Liu et al, 2022 ; Du et al, 2023 ; Brown et al, 2024 ) and reward prediction errors ( Hong et al, 2011 ; Chang et al, 2016 ; Sharpe et al, 2017 ). The phase resetting mechanism may allow inhibition associated with reward expectation to have a subtractive effect on the dopamine neuron's output firing rate ( Eshel et al, 2015 ), by translating inhibitory barrages into a slowed rate of phase advance.…”

Section: Discussionmentioning

confidence: 92%

Impact of Unitary Synaptic Inhibition on Spike Timing in Ventral Tegmental Area Dopamine Neurons

Higgs,

Beckstead

2024

eNeuro

View full text Add to dashboard Cite

Midbrain dopamine neurons receive convergent synaptic input from multiple brain areas, which perturbs rhythmic pacemaking to produce the complex firing patterns observed in vivo. This study investigated the impact of single and multiple inhibitory inputs on ventral tegmental area (VTA) dopamine neuron firing in mice of both sexes using novel experimental measurements and modeling. We first measured unitary inhibitory postsynaptic currents (uIPSCs) produced by single axons using both minimal electrical stimulation and minimal optical stimulation of rostromedial tegmental nucleus (RMTg) and ventral pallidum (VP) afferents. We next determined the phase resetting curve (PRC), the reversal potential for GABAAreceptor-mediated IPSCs, and the average inter-spike membrane potential trajectory during pacemaking. We combined these data in a phase oscillator model of a VTA dopamine neuron, simulating the effects of unitary inhibitory postsynaptic conductances (uIPSGs) on spike timing and rate. The effect of a uIPSG on spike timing was predicted to vary according to its timing within the inter-spike interval (ISI), or phase. Simulations were performed to predict the pause duration resulting from synchronous arrival of multiple uIPSGs, and the changes in firing rate and regularity produced by asynchronous uIPSGs. The model data suggest that asynchronous inhibition is more effective than synchronous inhibition, because it tends to hold the neuron at membrane potentials well positive to the IPSC reversal potential. Our results indicate that small fluctuations in the inhibitory synaptic input arriving from the many afferents to each dopamine neuron are sufficient to produce highly variable firing patterns like those observed in vivo.Significance StatementThis study dissects the input-output relationship of VTA dopamine neurons receiving inputs from single presynaptic inhibitory neurons. We measured unitary IPSCs from two major inhibitory inputs (the RMTg and VP) and simulated their impact on dopamine neuron firing based on new experimental data including the phase resetting curve (PRC) and the reversal potential of the GABAAreceptor-mediated currents. The results predict the impact of single and multiple unitary inhibitory postsynaptic conductances (uIPSGs) on spike timing and suggest that asynchronous, low-frequency inhibition can summate in a supralinear manner to powerfully slow or halt a dopamine neuron's firing.

show abstract

Section: Discussionmentioning

confidence: 92%

Impact of Unitary Synaptic Inhibition on Spike Timing in Ventral Tegmental Area Dopamine Neurons

Higgs,

Beckstead

2024

eNeuro

View full text Add to dashboard Cite

show abstract

“…We identified that IPN GAD2 neurons send extensive projections to the hindbrain, including the LDTg area, as previously reported for IPN neuronal subtypes 23 , 27 . The LDTg send abundant excitatory and inhibitory inputs to the VTA that control DA neuron burst firing and reward processing 24 , 43 , 44 . Recent work indicates the IPN inhibits LDTg neurons projecting to the VTA to control nicotine aversion 41 , and our current findings demonstrate that the IPN GAD2 →LDTg circuit regulates NP by modulating DA signals.…”

Section: Discussionmentioning

confidence: 99%

“…Optically evoked IPSCs in LDTg cholinergic neurons were at least partially blocked by a GABA A receptor antagonist and all inhibitory currents were carried by chloride providing a potential mechanism by which IPN inhibitory input reduces activity of cholinergic LDTg neuron that innervate the VTA to potentially reduce VTA DA activity. However, mesolimbic DA and motivational behaviors are also controlled by separate LDTg GABA and glutamatergic populations that directly or indirectly project to the VTA 44 . Thus, we cannot exclude the possibility that the IPN also innervates LDTg GABAergic and/or glutamatergic neurons to modulate aversive and motivational behaviors, a topic that requires future study.…”

Section: Discussionmentioning

confidence: 99%

Dopamine control of social novelty preference is constrained by an interpeduncular-tegmentum circuit

Molas,

Freels,

Zhao-Shea

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Animals are inherently motivated to explore social novelty cues over familiar ones, resulting in a novelty preference (NP), although the behavioral and circuit bases underlying NP are unclear. Combining calcium and neurotransmitter sensors with fiber photometry and optogenetics in mice, we find that mesolimbic dopamine (DA) neurotransmission is strongly and predominantly activated by social novelty controlling bout length of interaction during NP, a response significantly reduced by familiarity. In contrast, interpeduncular nucleus (IPN) GABAergic neurons that project to the lateral dorsal tegmentum (LDTg) were inhibited by social novelty but activated during terminations with familiar social stimuli. Inhibition of this pathway during NP increased interaction and bout length with familiar social stimuli, while activation reduced interaction and bout length with novel social stimuli via decreasing DA neurotransmission. These data indicate interest towards novel social stimuli is encoded by mesolimbic DA which is dynamically regulated by an IPN→LDTg circuit to control NP.

show abstract

The mesopontine tegmentum in reward and aversion: From cellular heterogeneity to behaviour

Bastos-Gonçalves,

Coimbra,

Rodrigues

2024

Neuroscience & Biobehavioral Reviews

View full text Add to dashboard Cite

Dopamine release and negative valence gated by inhibitory neurons in the laterodorsal tegmental nucleus

Cited by 8 publications

References 79 publications

Impact of Unitary Synaptic Inhibition on Spike Timing in Ventral Tegmental Area Dopamine Neurons

Impact of Unitary Synaptic Inhibition on Spike Timing in Ventral Tegmental Area Dopamine Neurons

Dopamine control of social novelty preference is constrained by an interpeduncular-tegmentum circuit

The mesopontine tegmentum in reward and aversion: From cellular heterogeneity to behaviour

Contact Info

Product

Resources

About