Table 1.

Methods of inactivation

Method	Mechanism	Penetrance	Characteristics
Lesions	Irreversible removal of neural tissue [87]	High Dependent on how completely the target brain area is removed [88]	Compensatory plasticity [88,89] Damage to fibres of passagea [90] Degeneration of upstream areas (e.g., thalamus) [88]
Pharmacological	Activation of inhibitory neurons via reagents [82]	Moderate Dependent on ligand diffusion [82]	Area of effect relies on diffusion of reagent which may vary between reagents (e.g., muscimol spreads maximally and γ-aminobutyric acid [GABA] minimally) [82] Difficult to apply to certain brain areas
Cooling	Reduction of cortical temperature to reduce spiking [21]	Moderate Dependent on temperature conduction through tissue [7,8]	Slow but sustained control of inactivation [88] Area of effect is dependent on the size of the cooling loop/probe [21] Can cool nontarget areas via cooled blood vessels [21]
Chemogenetics	Activation of receptors, genetically expressed in target neurons, via ligands [9]	Low to moderate Dependent on delivery, either viral vector or transgenic animals [23,81]	Area of effect is dependent on both diffusion of ligand and expression of receptor [79]
Optogenetics	Activation of photoreceptors, genetically expressed in target neurons, via light [79]	Low to moderate Dependent on delivery, either viral vector [91] or transgenic animals [79] Differential expression between species [79]	Rapid control of inactivation [92] Area of effect is dependent on both spread of light delivery and expression of receptors [79] Cell specificity mostly restricted to mouse model [93] Controls needed against heat generation from light application [92]

^aExcitotoxic lesions which spare fibres of passage.