The video discusses a surgical procedure for implanting bone screws in a mouse's skull. It covers preparation steps, locating screw placement, scoring the skull, and applying liquid cyanoacrylate to secure the screws while avoiding damage to the underlying dura, ensuring the success of the micro drive implant.

surgical implantation of the micro-drive on the mouse skull

Micro-Drive Implant for Recording Daily Neural Activity in Juvenile Mice

The brain undergoes large-scale changes during the critical developmental windows of childhood and adolescence1,2,3. Many neurologic and psychiatric diseases, including autism and schizophrenia, first manifest behaviorally and biologically during this period of juvenile and adolescent brain development4,5,6. While much is known regarding the cellular, synaptic, and genetic changes that occur across early development, comparatively little is known regarding how circuit- or network-level processes change throughout this time window. Importantly, circuit-level brain function, which ultimately underlies complex behaviors, memory, and cognition, is a non-predictable, emergent property of cellular and synaptic function7,8,9,10. Thus, to fully understand network-level brain function, it is necessary to directly study neural activity at the level of an intact neural circuit. In addition, to identify how brain activity is altered throughout the progression of neuropsychiatric disorders, it is critical to examine network activity in a valid disease model during the specific temporal window when the behavioral phenotypes of the disease manifest and to track the observed changes as they persist into adulthood.
One of the most common and powerful scientific model organisms is the mouse, with large numbers of unique genetic strains that model neurodevelopmental disorders with age-dependent onset of the behavioral and/or mnemonic phenotypes11,12,13,14,15,16,17,18,19,20,21. While it is challenging to correlate precise developmental time points between the brains of humans and mice, morphological and behavioral comparisons indicate that p20-p21 mice represent the human ages of 2-3 years old, and p25-p35 mice represent the human ages of 11-14 years old, with mice likely reaching the developmental equivalent of a human 20 year old adult by p603,22. Thus, to better understand how the juvenile brain develops and to identify how the neural networks of the brain become dysfunctional in diseases like autism or schizophrenia, it would be ideal to directly monitor brain activity in vivo in mice across the ages of 20 days to 60 days old.
However, a fundamental challenge in monitoring brain activity across early development in mice is the small size and relative weakness of juvenile mice. The chronic implantation of electrodes, which is necessary for longitudinal studies of brain development, typically requires large, bulky housing to protect the fine electrode wires and interface boards23,24, and the implants must be firmly attached to the mouse skull, which is thinner and less rigid in young mice due to reduced ossification. Thus, virtually all studies of in vivo rodent physiology have been performed in adult subjects due to their relative size, strength, and skull thickness. To date, most studies exploring in vivo juvenile rodent brain physiology have been performed in wild-type juvenile rats, which necessarily limits the ability to experimentally monitor juvenile brain function in a freely behaving model of a human disorder25,26,27,28,29,30.
This manuscript describes novel implant housing, a surgical implantation procedure, and a post-surgery recovery strategy to chronically study the long-term (up to 4 or more weeks) in vivo brain function of juvenile mice across a developmentally critical time window (p20 to p60 and beyond). The implantation procedure allows for the reliable, permanent affixation of the electrodes to the skulls of juvenile mice. Furthermore, the micro-drive design is lightweight, as this micro-drive weighs ~4-6 g when fully assembled, and due to the minimal counterbalancing required to offset the weight of the implant, it does not impact the behavioral performance of juvenile mice during typical behavioral paradigms.

Author Spotlight: A Lightweight Drive Implant for Chronic Tetrode Recordings in Juvenile Mice  

A Lightweight Drive Implant for Chronic Tetrode Recordings in Juvenile Mice

We're interested in understanding how the brain operates at a network level. This method is our attempt to explore the development of brain networks to identify developmental alterations in age dependent diseases like autism, schizophrenia or bipolar disorder. The silicon probe technology provides a simpler, more consistent method to record network activity in vivo.But despite this, chronic tetra recordings do offer some advantages over silicon probes, such as simultaneously recording over a broader spatial distribution of brain regions. Chronic recordings pose a unique challenge to in vivo electrophysiology due to several factors, including gliosis at the recording sites, movement of the recording site over time or failure of the attachment method. Our recent work demonstrated that the sweeps encoded by the theta oscillation of the hippocampus during active movement of the animal every hundred milliseconds or so iteratively cycle forward, prospectively evaluating possible future states and backwards retrospectively evaluating prior actions.Performing these in vivo recordings in juvenile mice poses several engineering challenges due to the small size of the mice, their relative weakness and the lack of development in their skull. Our methodology overcomes these limitations and allows us to chronically record network level activity daily in the developing mouse brain. Besides recording chronically in juvenile mice, our method allows us to record from up to 16 distinct bilateral brain regions irrespective of the spatial relationship of those regions.These developments will allow us to identify how networks establish functional communication across developments, both in the healthy brain and in mouse models of neurodevelopmental disorders, like autism spectrum disorders.

Watch this Scientific Journal Video about Surgical Implantation of the Micro-Drive on the Mouse Skull at JoVE.com

Surgical Implantation of the Micro-Drive on the Mouse Skull  

After preparing the mouse for surgery and exposing the skull, place the bone screws in the extreme lateral, rostral or caudal portions of the skull where the bone is thickest and the bone screws are sufficiently far away from the micro drive implant. Use a scalpel blade or drill bit to score the skull near the bone screw hole locations, providing a rough surface for the liquid cyanoacrylate to bind. Then thread each bone screw into place, careful not to pierce the underlying dura.Using a sterile 30-gauge needle, apply liquid cyanoacrylate around each bone screw, thickening the skull where the bone screws have been attached. Ensure that no cyanoacrylate enters the exposed dura above the recording sites.

surgical-implantation-of-the-micro-drive-on-the-mouse-skull

Research

JoVE Journal

Neuroscience

517 Views.  UT Southwestern Medical Center. After preparing the mouse for surgery and exposing the skull, place the bone screws in the extreme lateral, rostral or caudal portions of the skull where the bone is thickest and the bone screws are sufficiently far away from the micro drive implant. Use a scalpel blade or drill bit to score the skull near the bone screw hole locations, providing a rough surface for the liquid cyanoacrylate to bind. Then thread each bone screw into place, careful not to pierce the underlying dura.Using...