. Author manuscript; available in PMC: 2020 Oct 23.

Published in final edited form as: Mol Psychiatry. 2020 Feb 21;25(11):2742–2758. doi: 10.1038/s41380-020-0685-9

Table 1:

Overview of studies using optogenetic/chemogenetic techniques in real-time to manipulate mPFC circuitry in studies of anxiety and depression

	Neuromodulatory approach	Target Population	Effect	Test
Soma Targeting
Covington, 2010⁷⁵	ChR2; 40ms of 100hz per 3 second period, 1–2mW	Glutamatergic and GABAergic	Antidepressant	Social avoidance, SPT
Covington, 2010⁷⁵	ChR2; 40ms of 100hz per 3 second period, 1–2mW	Glutamatergic and GABAergic	No effect	EPM
Lee, 2015⁷⁶	ChR2; 5ms 10hz, 1mW	Glutamatergic	Antidepressant	Social avoidance
Warden, 2012⁶⁴	ChR2; 5ms 20hz, 3mW	Glutamatergic	No effect	FST
Yizhar, 2011⁷⁸	SSFO; light delivery produces asynchronous excitability enhancement	Glutamatergic	Pro-depressive	Social exploration
Yizhar, 2011⁷⁸		Parvalbumin	No effect	Social exploration
Perova, 2015¹⁰²	Gi DREADD; 10mg/kg CNO prior to training and testing	PL Parvalbumin neurons	Pro-depressive	Learned helplessness
Adhikari, 2015⁹⁸	Chr2; 5ms 1mW, 10Hz	vmPFC Glutamatergic	No effect	OFT, EPM
Ferenczi, 2016⁷⁷	SSFO; light delivery produces asynchronous excitability enhancement	Glutamatergic	Pro-depressive	SPT, Social exploration
Warthen, 2016⁷⁹	Gq DREADD, 0.5–2.5mg/kg CNO	Glutamatergic	No effect	Social exploration, OFT
Son, 2018⁶⁷	ChR2; 1 second 100hz per 4 second period	vGluT2	Antidepressant	TST
Soumier, 2014¹⁰¹	Gi DREADD; 5mg/kg CNO	PL Somatostatin neurons	Pro-depressive	Test battery net result
Kumar, 2013⁶⁵ – this manipulation produced a locomotor effect	ChR2; Neuron matched (~4hz), 2mW	PL mPFC Thy-1	Antidepressant	FST
Carreno, 2016⁶⁶	Gq DREADD; 0.5mg/kg CNO	mPFC neurons that receive vHIPP input	Antidepressant	FST
Afferent Targeting
Felix-Ortiz, 2016⁸⁰	ChR2; 5ms 5mW, 20hz	BLA - mPFC	Anxiogenic, Pro-depressive	EPM, OFT, Social exploration
Felix-Ortiz, 2016⁸⁰	NpHR; 5mW, constant	BLA - mPFC	Anxiolytic, Antidepressant	OFT, Social exploration
Chaudhury, 2013⁸²	NpHR; 8 seconds on - 2 seconds off	VTA - mPFC	Pro-depressive, No effect	Social avoidance, SPT
	Chr2, 0.5hz 15ms and 20hz 40ms	VTA - mPFC	No effect	Social avoidance, SPT
Padilla-Coreano, 2016¹⁰⁰	Arch; Continuous, 10 mW, 2 minutes off – 2 minutes on	vHIPP - mPFC	Anxiolytic	EPM, OFT, NSF
Padilla-Coreano, 2016¹⁰⁰	Arch; Continuous, 10 mW, 2 minutes off – 2 minutes on	MDT - mPFC	No effect	EPM
Carreno, 2016⁶⁶ – some effects observed from ketamine antidepressant baseline	ChR2; 20hz for 10 minutes, 30mW	vHIPP - mPFC	Antidepressant with DRN inactivation	FST
	eNpHR3.0; Continuous, 10 minutes	vHIPP - mPFC	Pro-depressive	FST
	eNpHR3.0; Continuous, 10 minutes	MDT - mPFC	No effect	FST
Miller, 2017⁶⁹	Gq DREADD; 1mg/kg CNO	MDT - mPFC	Antidepressant	FST, TST
Efferent Targeting
Warden, 2012⁶⁴	ChR2; 5ms 20hz, 10–20mW	mPFC - DRN	Antidepressant	FST
Warden, 2012⁶⁴	ChR2; 5ms 20hz, 10–20mW	mPFC - LHB	Pro-depressive	FST
Adhikari, 2015⁹⁸	Chr2; 5ms 10Hz, 10mW	vmPFC - BMA	Anxiolytic	OFT, EPM
Adhikari, 2015⁹⁸	eNpHR3.0; 10mW	vmPFC - BMA	Anxiogenic	OFT, EPM
Bagot, 2015⁸⁷	ChR2; 4hz, 15–20mW	mPFC - NAc	Antidepressant	Social avoidance
Bagot, 2015⁸⁷	ChR2; 4hz, 15–20mW	mPFC - NAc	No effect	OFT
Hultman, 2016⁸⁶	Gq DREADD; 1mg/kg CNO	mPFC – amygdala	Antidepressant	Social avoidance
Challis, 2014⁸⁸ – this manipulation was performed during the social defeat sensory contact period not testing	ChR2; 25hz, 10 ms, for 10 minutes, 10mW	PL mPFC - DRN	Pro-depressive	Social avoidance
	Arch; 20 minutes continuous, 10mW	PL mPFC - DRN	Antidepressant	Social avoidance
Carlson, 2017⁶⁸	ChETA; Closed loop, gamma bursts timed to IL oscillations	IL mPFC - MDT and MDT soma	Antidepressant	TST
	ChETA; Gamma bursts not timed to IL oscillations	IL mPFC - and MDT soma	No effect	TST
	ChETA, 14hz	IL mPFC - and MDT soma	Pro-depressive	TST
Dolzani, 2018⁷⁴ – effects observed from ketamine antidepressant baseline	Real-time, Gi DREADD; 3mg/kg CNO during exposure to uncontrollable stress	PL - DRN	Pro-depressive	Social exploration

Anterior cingulate cortex (ACC), basolateral amygdala (BLA), basomedial amygdala (BMA), dorsal raphe nucleus (DRN), elevated plus maze (EPM), forced swim test (FST), infralimbic (IL), lateral habenula (LHB), medial dorsal thalamus (MDT), medial prefrontal cortex (mPFC), nucleus accumbens (NAc), novelty suppressed feeding (NSF), prelimbic (PL), somatostatin (SST), sucrose preference test (SPT), ventral hippocampus (vHIPP), ventral medial prefrontal cortex (vmPFC), ventral tegmental area (VTA), vesicular glutamate transporter (vGlut)