Learning and synaptic plasticity in 3D bioengineered neural tissues

•Non-associative learning responses were elicited in bioengineered neural tissues.•Upregulation of immediate early genes (IEG) were observed with distributed training.•Implications of studying fundamental features of cognition in vitro are discussed. Though neuroscientists have historically relied upon measurement of established nervous systems, contemporary advances in bioengineering have made it possible to design and build artificial neural tissues with which to investigate normative and diseased states [1–5] however, their potential to display features of learning and memory remains unexplored. Here, we demonstrate response patterns characteristic of habituation, a form of non-associative learning, in 3D bioengineered neural tissues exposed to repetitive injections of current to elicit evoked-potentials (EPs). A return of the evoked response following rest indicated learning was transient and partially reversible. Applying patterned current as massed or distributed pulse trains induced differential expression of immediate early genes (IEG) that are known to facilitate synaptic plasticity and participate in memory formation [6,7]. Our findings represent the first demonstration of a learning response in a bioengineered neural tissue in vitro.