Construction of Microdrive Arrays for Chronic Neural Recordings in Awake Behaving Mice

Summary

The design and assembly of microdrives for in vivo electrophysiological recordings of brain signals from the mouse is described. By attaching microelectrode bundles to sturdy driveable carriers, these techniques allow for long-term and stable neural recordings. The lightweight design allows for unrestricted behavioral performance by the animal following drive implantation.

Abstract

State-of-the-art electrophysiological recordings from the brains of freely behaving animals allow researchers to simultaneously examine local field potentials (LFPs) from populations of neurons and action potentials from individual cells, as the animal engages in experimentally relevant tasks. Chronically implanted microdrives allow for brain recordings to last over periods of several weeks. Miniaturized drives and lightweight components allow for these long-term recordings to occur in small mammals, such as mice. By using tetrodes, which consist of tightly braided bundles of four electrodes in which each wire has a diameter of 12.5 μm, it is possible to isolate physiologically active neurons in superficial brain regions such as the cerebral cortex, dorsal hippocampus, and subiculum, as well as deeper regions such as the striatum and the amygdala. Moreover, this technique insures stable, high-fidelity neural recordings as the animal is challenged with a variety of behavioral tasks. This manuscript describes several techniques that have been optimized to record from the mouse brain. First, we show how to fabricate tetrodes, load them into driveable tubes, and gold-plate their tips in order to reduce their impedance from MΩ to KΩ range. Second, we show how to construct a custom microdrive assembly for carrying and moving the tetrodes vertically, with the use of inexpensive materials. Third, we show the steps for assembling a commercially available microdrive (Neuralynx VersaDrive) that is designed to carry independently movable tetrodes. Finally, we present representative results of local field potentials and single-unit signals obtained in the dorsal subiculum of mice. These techniques can be easily modified to accommodate different types of electrode arrays and recording schemes in the mouse brain.

Introduction

The use of the microelectrode technique for recording extracellular neural signals in vivo has a long and valued tradition in neuroscience ^{1, 2}. The ability to record electrical activity from many brain regions in freely behaving animals is, however, a more recent technology that is becoming increasingly common as the software packages for the acquisition, analysis and discrimination of neural signals becomes more sophisticated and user-friendly ^{3, 4}. The technological advances on the software side have also been accompanied by reductions in the weight and bulk of the implantable devices, which have been scaled down sufficiently for re....

Protocol

1. Tetrode Fabrication

1. Start by using insulated 12.5 μm (0.0005") diameter core platinum-iridium wire from California Fine Wire. The length of the wire should be cut to the appropriate length for the target structure. For example, cut the wire to at least 30 cm long for targeting the dorsal subiculum or hippocampus.
2. Fold the wire over at the center so that there are two parallel wires which will be 15 cm in length. Drape the midpoint of this wire over a horizontal arm to form four parallel wires of 7.5 cm in length. Next attach the rubber-coated clip near the bottom of the draped wire, creating a bundle of four wires.
3. Place the rubbe....

Results

After implanting the microdrive and lowering the electrodes to the intended brain targets, an amplified data acquisition system, such as a Neuralynx Lynx-8, is needed for recording neural signals. Representative neural recordings of local field potentials (LFPs) and single-unit action potentials (often termed "spikes") from the mouse dorsal subiculum are shown in Figure 2. LFP signals were sampled at 3 kHz and band-pass filtered between 0.1-500 Hz (Figure 2A and 2B).......

Discussion

We have described a set of techniques for constructing light and compact microdrives for the recording of extracellular unit and field potential activity in mice. By building custom microdrives with bases fashioned from acrylic glass (methyl methacrylate), the core system can be easily adapted for multiple drives and for the targeting of a wide array of neural regions. We have successfully modified the system for recording from multiple brain targets and with larger arrays for recordings in mice. With further modif.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
0.0005" (12.5 μM) diameter Platinum-Iridium wire	California Fine Wire	CFW#100-167	HML VG insulated www.calfinewire.com
0.002" (50 μM) diameter Stableohm 675 wire	California Fine Wire	CFW# 100-188	HML insulated Ni-Cr
polyamide tubing	Polymicro Technologies	1068150020	99 micron I.D., 166 micron O.D. www.polymicro.com
brass guides	World Plastics Inc		3.3 x 6.6 mm
Delrin blocks	World Plastics Inc		3.13 x 2.5 mm
Fillister head brass screws	J.I. Morris Co.	00-90 x 1/2	drive screw www.jimorrisco.com
hex brass nuts	J.I. Morris Co.	00-90
Fillister head brass screws	J.I. Morris Co.	000-120 x 3/32	EIB mount and ground screw
plexiglass acrylic	Canal Street Plastics		5 mm thick, clear, www.cpcnyc.com
cyanoacrylate	Krazy Glue		2 g tube
electronic interface board	Neuralynx	EIB-18	www.neuralynx.com
non-cyanide gold solution	SIFCO	SIFCO 5355	www.sifcoasc.com
VersaDrive 4	Neuralynx		four tetrode model
tetrode assembly station	Neuralynx
motorized tetrode spinner	Neuralynx	tetrode spinner 2.0
VersaDrive jig	Neuralynx
soldering iron	Radio Shack	64-2802B	www.radioshack.com
nanoZ	Neuralynx
small bit drill/driver	Ram Products	Rampower 35	with footpedal controller, www.ramprodinc.com
drill bits	Small Parts, Inc.		3/32" bits, www.smallpartsinc.com
dissecting microscope	Olympus	SZ-60	www.olympusamerica.com
heat gun	Alphawire	Fit gun 3	use setting "1" only, www.alphawire.com
26 AWG copper wire	Arcor Electronics	F26	for ground wires, www.arcorelectronics.com
soldering flux	Eagle	2 oz, #205
0.02" diameter solder	Kester	24-6337-0010	www.kester.com
benchtop vise	Vacu-Vise	Model 300
fiber optic light	Nikon	MKII	dual light arms, www.nikon.com
5-min epoxy	Allied Electronics		25 ml, www.alliedelec.com
fine tweezers	Roboz Surgical Instrument Co.	RS-4907, RS-5010	INOX material, www.roboz.com
micro dissecting scissors	Roboz Surgical Instrument Co.	RS-5880
Table 1. Materials and reagents used for constructing tetrodes and microdrives.