Several novel strategies using engineered receptors activated by synthetic ligands or by light have recently ushered in a new era of brain research that allows for precise experimental manipulation of neuronal activity. These techniques are now being used to probe the involvement of discrete brain circuits in complex behaviors.

One such approach uses designer receptors exclusively activated by designer drugs (DREADDs) to modulate cellular functions (Rogan and Roth, 2011). This family of evolved muscarinic receptors has been shown to increase (Gs-DREADD; Gq-DREADD) or decrease (Gi/o-DREADD) cellular activity following administration of an otherwise inert synthetic ligand, clozapine-n-oxide (Armbruster et al, 2007). When packaged into viral vectors or expressed in transgenic mouse models, these tools allow cellular activity to be controlled in a defined spatial and temporal manner. For example, activation of hippocampal neurons by Gq-DREADD receptors amplifies γ-rhythms and increases locomotor activity and stereotypy in mice (Alexander et al, 2009). Activity of non-neuronal cells can also be controlled by DREADD receptors, as expression and activation of either Gs-DREADD or Gq-DREADD receptors in pancreatic β-cells increases insulin release, and repeated activation of these receptors leads to β-cell hypertrophy (Guettier et al, 2009).

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