a 12 h: 12 h light: dark cycle. All animals were held in a facility beside lab 1 week
prior to surgery, post-surgery and throughout the duration of the behavioral assays
to minimize stress from transportation and disruption from foot traffic. All proce-
dures were approved by the Animal Care and Use Committee of Harvard University
and conformed to US National Institutes of Health guidelines.
Stereotaxic surgery: After animals were acclimatized to the holding facility for
more than 1 week, they were anesthetized with a mixture of 60 mg/kg of ketamine
and 0.5 mg/kg medetomidine administered intraperitoneal injection, with 0.03 mL
update injections of ketamine to maintain anesthesia during surgery. A heating pad
(at 37 °C) was placed underneath the body to provide warmth during surgery.
Depth of anesthesia was monitored by pinching the animal’s feet periodically.
Animal was placed in a stereotaxic frame. 1 mm longitudinal incision was made
and skin was resected from the center axis of the skull to expose a 2 mm by 2 mm
portion of the skull. The dura was incised and resected from the surface of the skull.
Next, a 0.5 mm diameter hole was drilled into the frontal and parietal skull plates
using a dental drill. Sterile saline was swabbed on the brain surface to keep it moist
throughout the surgery. Stereotaxic arm was used to clamp needle containing the
injectable electronics. Mesh electronic was loaded into the glass needle with a
diameter of 100– 200 μm as described above. The glass needle was then mounted to
a patch-clamp setup and lowered approximately 1 mm into the skull (Interaural:
6.16 mm, Bregma:−3.84 mm) for injection. After injection, needle is drawn out of
the brain tissue and the I/O region was ejected on the surface of the skull.
After bonding withflexible cable by ACF bonding as described above, skins
retracted from the center axis were replaced and the incision was sealed with a
C&B-METABOND. Anti-inflammatory and anti-bacterial ointments were swabbed
onto the skin after surgery. A 0.3 mL intraperitoneal injection of Buprenex for
0.1 mg/kg was administered to reduce post-operative pain. Animals were observed
for four hours after surgery. Hydrogel was provided as food. Heating pad was used
to maintain a 37 °C warm bath for the remainder of post-operative care. All pro-
cedures complied with the United States Department of Agriculture guidelines for
the care and use of laboratory animals and were approved by the Harvard
University Office for Animal Welfare.
Incubation and behavioral analysis: Animal was cared for every day for
3 days after the surgery and every other day afterfirst 3 days. Animal was
administered with 0.3 mL of Buprenex (0.1 mg/kg, diluted with 0.5 mL PBS)
every 12 h for 3 days. Animal was also observed every other day for behavioral
changes. Animals, which were surgically operated on, were housed individually in
cage with food and water ad libitum. The room was maintained at constant tem-
perature on a 12–12 h light-dark cycle.
5.2 Experimental 71