Table 2.
Optogenetic tolls in the depression treatment performed in in vivo models published from 2013 to 2018
| Publication | Neuron Cell Population | Light Color | Stimulation Parameters | Photoactivatable Protein | Findings |
|---|---|---|---|---|---|
| Covington et al. 2010 [77] | Infralimbic and prelimbic mPFC regions | Blue (473 nm) | 40 ms 100 Hz (9.9 ms spike width), pulses every 3 s | ChR2 | Antidepressant-like effect detected by social interaction and sucrose preference tests |
| Warden et al. 2012 [78] | mPFC to dorsal raphe nucleus and lateral habenula | Blue (473 nm) | NR | ChR2 | (1) Increase in motivated scape behavior |
| (2) Increase in immobility in the FST | |||||
| Kumar et al. 2013 [80] | Layer V pyramidal neurons of the prelimbic region the mPFC | Blue (473 nm) | 40 Hz (5 ms pulse width) and 4.02 Hz, for 1 min | ChR2 | (1) Decreased immobility in the FST |
| Blue (473 nm) | Tonic (0.5 Hz) and phasic (20 Hz) stimulation. 5 spikes over each 10 s period | ChR2-eYFP | (2) Absence of significant changes on the open field | ||
| (3) No improvement found in the social interaction test | |||||
| (4) Therapeutic response correlates with increased synchrony among depression-relevant limbic regions | |||||
| Chadhury et al. 2013 [123] | VTA DA neurons projecting to the NAc and to the mPFC | Yellow (563 nm) | 8 s light on and 2 s light off | eYFP (control) | Enhanced phasic firing VTA neurons projecting to the NAc induced persistent depression-like symptoms (social avoidance and reduced sucrose preference) |
| Blue (473 nm) | 17.0 to 23.8 mW/mm2, constant | NpHR3.0-eYFP | |||
| ChR2-eYFP | |||||
| Tye et al. 2013 [125] | VTA DA neurons | Yellow (593 nm) | 8 light pulses at 30 Hz every 5 s, for 3 min. Except for anhedonia (30 min) | eYFP (control) | Bidirectional control VTA DA neurons immediately and bidirectionally modulates depression (induces or relieves) |
| NpHR3.0-eYFP | |||||
| Friedman et al. 2014 [126] | VTA DA neurons | Blue (470 nm) | Five pulses, 20 Hz every 10 s period. Pulses delivered for 20 min a day for five consecutive days | ChR2-eYFP | Excessive optogenetic activation of VTA DA neurons in susceptible mice reduced firing rate and increased K+ currents (self-tuning compensation) |
| eYFP (control) | |||||
| Walsh et al. 2013 [86] | VTA DA neurons | Blue (473 nm) | Tonic (0.5 Hz, 15 ms) or phasic (20 Hz, 40 ms) light stimulations. 5 spikes over each 10 s period | ChR2-eYFP | (1) Phasic optogenetic activation increases BDNF amounts in the NAc of socially stressed mice but not of stress naive mice |
| Yellow (561 nm) | 8 s light on and 2 s light off | eYFP (control) | |||
| NpHR3.0-eYFP | (2) The stress gating of BDNF signaling is mediated by CRF acting in the NAc | ||||
| Bargot et al. 2014 [127] | MSN connecting the vHIP, the mPFC and the AMY to the NAc | Blue (473 nm) | 1 Hz, 4 ms pulse width, 10 min | ChR2-eYFP | Attenuation of vHIP-NAc transmission by optogenetics-induced LTD is pro-resilient, whereas acute enhancement of this input is pro-susceptible. Stimulation of either mPFC or AMY afferents to the NAc yielded no result |
| eYFP (control) |
IE4/5: Immediate-early 4/5; ChR2: channelrhodopsin-2; FST, forced swim test; AAV, Adeno-associated virus; CaMKIIα, calcium/calmodulin-dependent protein kinase type II alpha chain; Thy1, thymus cell antigen 1; eYFP, enhanced yellow fluorescent protein; mPFC, medial pre-frontal cortex; VTA, ventral tegmental area; NAc, nucleus accumbens; DA, dopamine; MSN, medium spiny neurons; vHIP, ventral hippocampus; FST, forced swim test; VTA, ventral tegmental area; NAc, nucleus accumbens; DA, dopamine; LTD, long-term depression; vHIP, ventral hippocampus; HCN2, cyclic nucleotide gated channel 2; BDNF, brain-derived neurotrophic fator; CRF, corticotropin releasing fator; AMY, basolateral amygdala.