. 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 3:

mPFC circuitry impacting behaviors used to study anxiety and depression

Behavior	Target Population	Reference
Forced swim - Animal is placed in an inescapable beaker of water of sufficient depth to prevent contact with the bottom of the beaker. Time immobile during a short test is measured. Increased time immobile is interpreted as a passive coping strategy.	PL mPFC Thy1 IL mPFC Glutamatergic vmPFC Drd1 *vmPFC Drd1* - BLA** mPFC - DRN mPFC - LHB vHIPP - mPFC MDT - mPFC	Kumar, 2013⁶⁵ Fuchikami, 2015⁶⁰ Hare, 2019⁴⁷ Hare, 2019⁴⁷ Warden, 2012⁶⁴ Warden, 2012⁶⁴ Carreno, 2016⁶⁶ Miller, 2017⁶⁹
Tail suspension - Animal is suspended by the tail. Time immobile during a short test is measured. Increased time immobile is interpreted as behavioral despair or a passive coping strategy.	mPFC vGlut2 IL mPFC - MDT MDT - mPFC	Son, 2018⁶⁷ Carlson, 2017⁶⁸ Miller, 2017⁶⁹
Social avoidance - Experimental mice are placed into a cage with larger, more aggressive, conspecific and allowed to interact for a short period of time. This interaction is followed by an extended period of sensory contact without physical contact. The interaction and sensory contact are repeated over multiple days. On test, time spent investigating a novel animal separated by a mesh enclosure is measured. Reduced time investigating the novel animal is interpreted as evidence of social avoidance. Time investigating the novel animal may also be contrasted against time spent investigating the mesh enclosure without a target present.	mPFC Pl mPFC Glutmatergic PL mPFC - DRN mPFC – Nac mPFC - amygdala VTA - mPFC VTA - mPFC	Covington, 2010⁷⁵ Lee, 2015⁷⁶ Challis, 2014⁸⁸ Bagot, 2015⁸⁷ Hultman, 2016⁸⁶ Chaudhury, 2013⁸² Friedman, 2014
Social exploration/Juvenile exploration - Experimental mice are placed into a box with multiple chambers. In one chamber is a conspecific in a mesh enclosure. Reduced time spent investigating the conspecific is interpreted as evidence of abnormal social behavior. Investigation time may be contrasted against time spent investigating an empty enclosure.	mPFC Glutamatergic PL mPFC - DRN BLA - mPFC	Yizhar, 2011⁷⁸, Ferenczi, 2016⁷⁷ Dolzani, 2018⁷⁴ Felix-Ortiz, 2016⁸⁰
Sucrose preference/Sucrose consumption - Animals are habituated to a sucrose solution, typically 1–2%, prior to testing. On test animals are given free access to bottles containing sucrose and water. The amount of each liquid consumed are measured. Reduced sucrose consumption as a percentage of total liquid consumed is interpreted as evidence of anhedonia.	mPFC IL mPFC Glutamatergic mPFC Glutamatergic	Covington, 2010⁷⁵ Fuchikami, 2015⁶⁰ Ferenczi, 2016⁷⁷
Elevated plus maze - Animals are given access to a plus shaped arena elevated above the floor. Two opposing arms have walls (‘closed’), and two are ‘open”. Increased time spent in the open arms during the test is interpreted as reduced anxiety	PL mPFC Thy-1 PL mPFC SST vmPFC Drd1 vmPFC - BMA BLA – mPFC vHIPP – mPFC	Kumar, 2013⁶⁵ Soumier, 2014¹⁰¹ Hare, 2019⁴⁷ Adhikari, 2015⁹⁸ Felix-Ortiz, 2016⁶¹ Padilla-Coreano, 2016¹⁰⁰
Open field test - Animals are given access to a square enclosure and allowed to freely explore. Time spent in the center of the field is measured. Animals that spend more time exploring the center of the field as opposed to the periphery are interpreted as being less anxious.	vMPFC - BMA BLA – mPFC vHIPP - mPFC	Adhikari, 2015⁹⁸ Felix-Ortiz, 2016⁶¹ Padilla-Coreano, 2016¹⁰⁰
Novelty suppressed feeding - Food deprived animals are given access to a square enclosure with a piece of food in the center. Time spent to approach the food and take a bite is measured. Animals with shorter feeding latencies are interpreted as being less anxious.	ACC mPFC Thy-1 IL mPFC Glutamatergic vmPFC Drd1 *vmPFC Drd1* - BLA** vHIPP – mPFC	Barthas, 2015¹⁰⁸, 2017¹⁰⁷ Fuchikami, 2015⁶⁰ Hare, 2019⁴⁷ Hare, 2019⁴⁷ Padilla-Coreano, 2016¹⁰⁰

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) Manipulations in bold demonstrate sustained effects.