Electrical measurements from individual cells and synapses in large populations of animals would help reveal fundamental properties of the nervous system and neurological diseases (Bier 2005; Jones, Buckingham, and Sattelle 2005; Kaletta and Hengartner 2006; Lieschke and Currie 2007). Small model organisms like worms and larvae are strong candidates for such large-scale experiments (Yanik, Rohde, and Pardo-Martin 2011); however, current methods to measure electrical activity via patch-clamping methods in these tiny animals requires low-throughput and invasive dissections (Broadie and Bate 1993; Drapeau et al. 1999; Goodman et al. 1998). To overcome these limitations we present nano-SPEARs: nanoscale electrodes that can record electrophysiological activity in small animals without dissections. We designed our prototype device to measure muscle activity in the 1-mm long roundworm Caenorhabditis elegans and show the first extracellular recordings of body-wall muscle activity inside an intact worm. We also reconfigured the geometry of the chip to record from the freshwater cnidarian Hydra littoralis, showing that this platform can be expanded to other animal species. In addition to versatility, our measurement system is scalable, providing a path to high-throughput measurements and offering new screening capabilities for studying human diseases with small model animals. As an example, we establish the first electrophysiological phenotypes for C. elegans models for Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s disease (PD), and show that the PD phenotype can be partially rescued with the drug clioquinol (Tardiff et al. 2012). Together these results demonstrate that nano-SPEARs provide the core technology for scalable electrophysiology microchips that will enable high-throughput, in vivo studies of fundamental neurobiology and neurological diseases. (abstract adapted from Gonzales et al. 2016)