Optogenetic dissection of neural circuitry: from synaptic causalities to blue prints for novel treatments of behavioral diseases

Lüscher, Christian; Pascoli, Vincent; Creed, Meaghan C.

doi:10.1016/j.conb.2015.07.005

Cited by 38 publications

(30 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the striatal circuits involved in the progression of addiction, activation of the IL–NAc shell and striatal D2R-MSN indirect pathways are effective for inhibiting related behavioral expression. Indeed, natural protective mechanisms of the striatal indirect pathway have been described (Bock et al, 2013), and striatal circuit-selective restoration of synaptic transmission has been shown to normalize circuit functions and rescue animal behaviors (Lüscher et al, 2015). Therefore, circuit-specific modulations provide a promising key solution for the development of effective therapeutic interventions that ameliorate (or even cure) addiction at each step of the addiction processes.…”

Section: Resultsmentioning

confidence: 99%

Alterations in Striatal Circuits Underlying Addiction-Like Behaviors

Kim¹,

Lee²,

Yun³

et al. 2017

Molecules and Cells

View full text Add to dashboard Cite

Drug addiction is a severe psychiatric disorder characterized by the compulsive pursuit of drugs of abuse despite potential adverse consequences. Although several decades of studies have revealed that psychostimulant use can result in extensive alterations of neural circuits and physiology, no effective therapeutic strategies or medicines for drug addiction currently exist. Changes in neuronal connectivity and regulation occurring after repeated drug exposure contribute to addiction-like behaviors in animal models. Among the involved brain areas, including those of the reward system, the striatum is the major area of convergence for glutamate, GABA, and dopamine transmission, and this brain region potentially determines stereotyped behaviors. Although the physiological consequences of striatal neurons after drug exposure have been relatively well documented, it remains to be clarified how changes in striatal connectivity underlie and modulate the expression of addiction-like behaviors. Understanding how striatal circuits contribute to addiction-like behaviors may lead to the development of strategies that successfully attenuate drug-induced behavioral changes. In this review, we summarize the results of recent studies that have examined striatal circuitry and pathway-specific alterations leading to addiction-like behaviors to provide an updated framework for future investigations.

show abstract

Section: Resultsmentioning

confidence: 99%

Alterations in Striatal Circuits Underlying Addiction-Like Behaviors

Kim¹,

Lee²,

Yun³

et al. 2017

Molecules and Cells

View full text Add to dashboard Cite

show abstract

“…The use of optogenetics in transgenic animals has led to an immense leap forward in the understanding of brain function relevant to human conditions (Deisseroth ) and in the context of glutamatergic signaling (Lüscher et al . ). By implementing Cre‐driven expression of light‐gated ion channels and pumps, so called opsins, optogenetic stimulations can be regulated in a precise spatiotemporal manner in vivo (Han ).…”

mentioning

confidence: 97%

Validated multi‐step approach for in vivo recording and analysis of optogenetically evoked glutamate in the mouse globus pallidus

Viereckel

Konradsson-Geuken

Wallén-Mackenzie

2018

Journal of Neurochemistry

View full text Add to dashboard Cite

Precise quantification of extracellular glutamate concentrations upon neuronal activation is crucial for the understanding of brain function and neurological disorders. While optogenetics is an outstanding method for the correlation between distinct neurons and their role in circuitry and behavior, the electrochemically inactive nature of glutamate has proven challenging for recording upon optogenetic stimulations. This difficulty is due to the necessity for using enzyme-coated microelectrodes and the risk for light-induced artifacts. In this study, we establish a method for the combination of in vivo optogenetic stimulation with selective measurement of glutamate concentrations using enzyme-coated multielectrode arrays and amperometry. The glutamatergic subthalamic nucleus (STN), which is the main electrode target site in deep brain stimulation treatment of advanced Parkinson's disease, has recently proven opotogenetically targetable in Pitx2-Cre-transgenic mice and was here used as model system. Upon stereotactic injection of viral Channelrhodopsin2-eYFP constructs into the STN, amperometric recordings were performed at a range of optogenetic stimulation frequencies in the globus pallidus, the main STN target area, in anesthetized mice. Accurate quantification was enabled through a multi-step analysis approach based on self-referencing microelectrodes and repetition of the experimental protocol at two holding potentials, which allowed for the identification, isolation and removal of photoelectric and photoelectrochemical artifacts. This study advances the field of in vivo glutamate detection with combined optogenetics and amperometric recordings by providing a validated analysis framework for application in a wide variety of glutamate-based approaches in neuroscience.

show abstract

“…) and the influence it will have when combined with chemo‐genetics on the elucidation of circuit function and pathology (Luscher et al . ). Certainly we should expect a great expansion in our knowledge here which will impact upon how we view synaptic signalling and the relevance of circuit function to brain pathology.…”

Section: Concluding Commentsmentioning

confidence: 97%

Synaptic signalling and its interface with neuropathologies: snapshots from the past, present and future

Beart

2016

Journal of Neurochemistry

View full text Add to dashboard Cite

This 'Past to Future' Review as part of the 60th anniversary year of the Journal of Neurochemistry focuses on synaptic transmission and associated signalling, and seeks to identify seminal progress in neurochemistry over the last 10 years which has advanced our understanding of neuronal communication in brain. The approach adopted analyses neurotransmitters on a case by case basis (i.e. amino acids, monoamines, acetylcholine, neuropeptides, ATP/purines and gasotransmitters) to highlight novel findings that have changed the way we view each type of transmitter, to explore commonalities and interactions, and to note how new insights have changed the way we view the biology of degenerative, psychiatric and behavioural conditions. Across all transmitter systems there was remarkable growth in the identification of targets likely to provide therapeutic benefit and which undoubtedly was driven by the elucidation of circuit function and new vistas of synaptic signalling. There has been an increasing trend to relate signalling to disease, notably for Alzheimer's and Parkinson's disease and related conditions, and which has occurred for each transmitter family. Forebrain circuitry and tonic excitatory control have been the centre of great attention yielding novel findings that will impact upon cognitive, emotional and addictive behaviours. Other impressive insights focus on gasotransmitters integrating activity as volume transmitters. Exciting developments in how serotonin, cholinergic, l-glutamate, galanin and adenosine receptors and their associated signalling can be beneficially targeted should underpin the development of new therapies. Clearly integrated, multifaceted neurochemistry has changed the way we view synaptic signalling and its relevance to pathobiology. Highlighted are important advances in synaptic signalling over the last decade in the Journal of Neurochemistry. Across all transmitter systems elucidation of circuit function, and notably molecular insights, have underpinned remarkable growth in the identification of targets likely to provide therapeutic benefit in neuropathologies. Another commonality was wide interest in forebrain circuitry and its tonic excitatory control. Increasingly observations relate to signalling in disease and behavioural conditions. This article is part of the 60th Anniversary special issue.

show abstract

Optogenetic dissection of neural circuitry: from synaptic causalities to blue prints for novel treatments of behavioral diseases

Cited by 38 publications

References 56 publications

Alterations in Striatal Circuits Underlying Addiction-Like Behaviors

Alterations in Striatal Circuits Underlying Addiction-Like Behaviors

Validated multi‐step approach for in vivo recording and analysis of optogenetically evoked glutamate in the mouse globus pallidus

Synaptic signalling and its interface with neuropathologies: snapshots from the past, present and future

Contact Info

Product

Resources

About