Biochemically functionalized probes for cell-type–specific targeting and recording in the brain

Abstract

Selective targeting and modulation of distinct cell types and neuron subtypes is central to understanding complex neural circuitry and could enable electronic treatments that target specific circuits while minimizing off-target effects. However, current brain-implantable electronics have not yet achieved cell-type specificity. We address this challenge by functionalizing flexible mesh electronic probes, which elicit minimal immune response, with antibodies or peptides to target specific cell markers. Histology studies reveal selective association of targeted neurons, astrocytes, and microglia with functionalized probe surfaces without accumulating off-target cells. In vivo chronic electrophysiology further yields recordings consistent with selective targeting of these cell types. Last, probes functionalized to target dopamine receptor 2 expressing neurons show the potential for neuron-subtype–specific targeting and electrophysiology.