The DREAM Implant: A Lightweight, Modular, and Cost-Effective Implant System for Chronic Electrophysiology in Head-Fixed and Freely Behaving Mice

Our research uses virtual reality tasks and chronic electrophysiology in mice and macaques to study naturalistic decision-making and rule learning. We focus on interactions between the anterior cingulate cortex and sensory regions like the visual cortex. And this approach aims to understand species-specific or generalizable computational strategies in goal-directed behaviors.

I think as a field, we're starting to recognize that if we want to truly understand neural computation, we have to do it while animals engage in behaviors that are meaningful and natural to them. So if we also want to record neuronal activity at the same time, what we need are implants that are both robust and also comfortable to wear for our animals. Technically, I think the biggest challenge is still to get high-yield neuronal recordings while also animal-engaged in complex behaviors.

And more generally, I think it's very important that electrophysiology becomes more accessible for labs that maybe have less funding or fewer technical resources so that we can level the playing field for great ideas to be turned into great experiments no matter which lab you work in. Our lab directly compares the neuronal and behavioral measurements of mice and monkeys doing the exact same naturalistic virtual environment foraging tasks. And by doing that, what we found is that actually a lot of the computational dynamics and the behavioral states they experience are directly the same.

The DREAM implant is the combination of the advantages that already exist in the field. It is lightweight and compact while also being modular, flexible in electrode placement, and features a recoverable microdrive, lowering the experimental cost. To begin, solder a 0.05 inch solder tail socket to the ground wire of the silicone probe.

Turn the screw on the microdrive body such that the microdrive shuttle is entirely retracted upwards. Lay the microdrive horizontally onto the microdrive holder. Place a small piece of adhesive putty on the microdrive holder.

Then, place a tiny drop of silicone plaster onto the shuttle. Place the probe with the flex cable onto the shuttle of the microdrive. Then, gently pull the flex cable toward the top of the microdrive until the bottom edge of the cable meets the bottom edge of the microdrive shuttle.

Place the headstage connector of the probe onto the adhesive putty at the top of the holder. Use a 27-gauge needle or a microbrush, to apply a small drop of cyanoacrylate glue between the electrode body and shuttle, avoiding the flex cable. Attach the amplifier to the crown ring using silicone plaster.

Then, attach the flex cable to the amplifier and cover the connection and cable in a thin layer of silicone plaster. Fasten the copper mesh cutout onto the Faraday cage with small drops of epoxy resin. To begin, place all sterile surgical instruments onto the sterile working platform.

Disinfect the shaved area of the anesthetized mouse multiple times with an iodine-based disinfectant and alcohol using cotton swabs. Place the mouse in a stereotactic frame using ear bars and a nose holder. Perform a paw pinch to confirm the depth of anesthesia.

Using small surgical scissors, cut an almond-shaped opening in the skin on top of the skull, reaching from just the posterior of the lambda suture to between the eyes. Continue cutting to remove the subcutaneous membrane and periosteum. Then, scratch the skull with a scalpel blade to remove soft membrane tissue.

Carefully scratch in a crisscross pattern with the tip of the scalpel turned upside down to roughen the surface of the skull. Alternate between a scalpel blade and sterile cotton buds to gently scratch and push away neck muscles attached to the sides of the lambda suture until the muscles are pushed back to the edge of the skull on top of the cerebellum. Use a 1 milliliter syringe to apply a small drop of cyanoacrylate glue between the skin and skull edges.

Apply dental cement primer across the skull for extra adhesion and harden with ultraviolet light. Find the target location for the probe implantation relative to bregma or lambda and outline the craniotomy around it with a surgical marker. Secure the headplate on the skull using dental cement.

With a dental drill, drill a small burr hole the width of the header pins over the brain areas. Drip the sterile saline onto the craniotomy using a syringe and remove it with non-shedding wipes. Gently insert a ground pin into each craniotomy and apply cement around the header pins.

Then, drill the outline of a larger craniotomy by moving around the edge in steady movements. To test the resistance of the drilled-out portion of the bone, gently push on it with fine forceps. Place the microdrive with silicon probe into the microdrive holder.

Angle the stereotax arm to reach the desired target brain area. Place the crown ring with the attached amplifier onto the three vertical pins at the rear of the microdrive holder. Lower the microdrive to within approximately 0.5 millimeters of the craniotomy, then use forceps to connect the ground or reference header pins.

Position the stereotactic arm with the microdrive over the craniotomy. Lower the microdrive until the probe shank touches the dura in the target area. Cement the base of the microdrive in place.

Cover the space between the base and skull with dental cement. Then, lower the silicon probe onto the brain. When the probe shanks touch the brain, quickly lower the probe by approximately 250 micrometers.

Once the probe is broken through the surface of the cortex, lower it at a slower pace. Using a 1 milliliter syringe, dispense a small drop of silicon elastomer into the craniotomy. Cover the silicone elastomer with an equal mixture of bone wax and mineral oil.

When the dental cement is solidified, loosen the microdrive holder with an Allen key. Gently retract the holder by approximately 1 centimeter, such that the microdrive is freestanding and the probe amplifier or connector remains fixed to the implant holder without stretching the flex cable. Place the pre-made crown and Faraday mesh around the headplate by stretching the cage at the opening and slotting it over the microdrive and flex cable horizontally.

Then, fix it onto the headplate with dental cement. Put the Faraday crown ring with probe connector or headstage over the crown, aligning the integrated holder for the probe amplifier or connector with the area marked by an indented X on the Faraday crown. Secure the ring to the Faraday cage with a drop of dental cement at each spoke ring junction.

Once secured, fully retract the stereotactic arm with the microdrive holder. Connect the probe amplifier or connector to the recording hardware and start a neuronal signal recording. If the probe has not yet reached its target location, slowly turn the microdrive screw counterclockwise to lower the probe while monitoring neuronal signals.

When neuro local field potentials are visible across the probe, end the test recording and disconnect the headstage connector. Cover the Faraday cage with self-adherent veterinary wrap.