Big Brains

I build tools to interrogate cephalopod systems and leverage independent parallel evolution of big brains in "human vs octopus" to reveal basic principles and novel solutions in brains

I  am interested in using functional comparisons of components and circuits in large sophisticated brains of vertebrates vs cephalopods to reveal basic principles and novelty in complex neural design. I have long-standing projects to establish and advance genetic tools (see injection, mRNA, and CRISPR images), genomic resources, advanced imaging (see brain image and beating hearts gif), and culturing techniques in cephalopods, and more specifically to develop pygmy squid and/or pygmy octopus into research lab models that enable direct experimental cephalopod-vertebrate comparisons, with a greater comparative context to the human brain. Mechanosensory and possibly ultrasound-sensitive ion channels in skin (see octopus hatchling gif - pigment flash matches 100 ms ultrasound stim) - and part of giant axon-jet propulsion, chromatophore-neuromuscular dynamic skin color / camouflage systems, or lateral line - are of particular interest.

Pygmy squid are the world's smallest cephalopods from egg to adult (see pink plants gif - the pink plastic leaves are around 1.5 inches - and the pygmy squid is able to attached with a glue gland on its back - in nature, it would be attached to sea grass or mangrove roots or rocks etc) and uniquely offer egg and larval sizes and transparencies similar to zebrafish (see two hatchling gifs). A target comparative experiment would be whole-brain light sheet calcium or voltage imaging of zebrafish vs pygmy squid hatchlings using an identical setup and mechanical/ultrasound or light stimulation to characterize circuits, with behavioral readouts in the chromatophore-neuromuscular dynamic skin color / camouflage system (see octopus video for chromatophore response to ultrasound - work done with Uri Magaram in the Chalasani Lab). To achieve this, I am lead on an international collaboration to sequence the pygmy squid genome, including upcoming single-cell sequencing work. Working in the past with Phillip Keller's lab at Janelia (see beating hearts gif), I adapted use of zebrafish light sheet imaging protocols to pygmy squid. Through an HFSP-funded collaboration with the lab of George Debregas at the Sorbonne Universite Laboratorie Jean Perrin in Paris, we have built a light sheet microscopy system specifically for pygmy squid and zebrafish, including dual electrophysiology capabilities - though it has gone untested for pygmy squid due to the pandemic. Critical challenges for the coming year include establishing breeding colonies, a more rapid injection protocol (see gif), and demonstration of GCaMP whole-brain imaging.

I have funded my research in cephalopods with grants from NIH, Human Frontiers In Science, and others. I have active collaborations with top researchers around the world.