Optogenetics in preclinical neuroscience and psychiatry research: recent insights and potential applications

Figures & data

Table 1 Summary of noteworthy opsin proteins commonly used in optogenetic research

Role	Opsin	Wavelength (nm)	Comments	Reference
Excitatory	ChR1	500	Original opsin. Not conventionally used.	^Citation13
	ChR2	473	Suitable for stimulation paradigms <40 Hz.	^Citation14
	ChETA*	500	ChR2 variant. Spike fidelity up to 200 Hz. Red-shifted variant exists.	^Citation12
	CatCh	474	Ca^2+-permeable ChR2 variant. 2.5× more photocurrent, 70× more light-sensitive, and higher frequency fidelity than ChR2.	^Citation128
	C1V1	560	Red-shifted chimeric opsin with full spectrum separation from ChR2.	^Citation21
	SFO*	470/561	Prolonged depolarizing effect with single light-pulse activation (470 nm) and termination (561 nm).	^Citation20,Citation21
Inhibitory	iC1C2/ChloC	475/465	Chloride-conducting ion channel.	^Citation26,Citation27
	eNpHR3.0	590	Chloride pump. Can potentially disrupt chloride gradient and cause post-inhibitory excitatory states.	^Citation22,Citation24
	eArch3.0	560	Proton pump.	^Citation16,Citation129
Cell signaling	OptoXR	500	Chimeric proteins in which G-protein coupled receptors are sensitive to light. Currently available with adrenergic (Gq, Gs) and serotonergic (Gi/o) receptors.	^Citation30,Citation31

Note:

* Variants of these opsins have different spectral absorption peaks.

Abbreviations: ChR, channelrhodopsin; eNpHR3.0, halorhodopsin; eArch3.0, archaerhodopsin; SFO, step function opsin.

Table 2 Contribution of various brain regions and circuits to the expression of depression-like symptoms

Neuronal population	Contribution	Behavioral model	Species	Reference
PFC	Antidepressant	Forced swim test	Mouse	^Citation47
PFC	Antidepressant	Social defeat	Mouse	^Citation49
PFC	None	Forced swim test	Rat	^Citation48
PFC-DRN	Antidepressant	Forced swim test	Rat	^Citation48
PFC-DRN	Prodepressant	Social defeat	Mouse	^Citation46
DRN (GABA)	Prodepressant	Social defeat	Mouse	^Citation57
VTA (dopamine)	Antidepressant	Forced swim	Rat	^Citation61
VTA (dopamine)	Antidepressant	Chronic stress	Mouse	^Citation61
VTA (dopamine)	Prodepressant	Social defeat	Mouse	^Citation62
VTA-NAcc	Antidepressant	Social defeat	Mouse	^Citation62
VTA-mPFC	None	Social defeat	Mouse	^Citation62

Notes: This table is a summary of studies that used optogenetic methodology to test depression circuitry. “Antidepressant” cell populations are those in which stimulation produces antidepressant-like behavioral effects and/or inhibition of which reduces these measures; “prodepressant” populations produce the opposite pattern of responses. Because of the equivocal findings of these studies, details are presented on behavioral model and species tested.

Abbreviations: PFC, prefrontal cortex; DRN, dorsal raphe nucleus; GABA, gamma-aminobutyric acid; mPFC, medial prefrontal cortex; NAcc, nucleus accumbens; VTA, ventral tegmental area.

Figure 1 Schematic depiction of brain circuits controlling anxiety.

Notes: Recent studies utilizing optogenetic approaches have implicated discrete populations of neurons and neural projections in anxiety disorders. Circles represent populations of neurons that have been targeted with optogenetic manipulations. Anxiogenic populations are represented in red, anxiolytic in blue, and populations producing no effect in white. Experiments in which opsins were targeted to genetically-defined cell populations are indicated by the relevant cell type listed within the circle. The presence or absence of projections from these neurons (circles) in the figure indicates whether the represented experiment targeted optical manipulations at terminals or cell bodies, respectively.
Abbreviations: BLA, basolateral amygdala; BNST, bed nucleus of the stria terminalis; CEA, central nucleus of the amygdala; CRF R2, corticotropin-releasing factor receptor 2; D1R, dopamine receptor D1; GABA, gamma-aminobutyric acid; Glu, glutamate; HIPP, hippocampus; hypothal, hypothalamus; LS, lateral septum; mPFC, medial prefrontal cortex; oxy, oxytocin; VTA, ventral tegmental area.

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