A brain slice is a thin section of living tissue prepared in a laboratory, providing a window into the brain’s intricate wiring. This technique allows neuroscientists to study neurons and their circuits in isolation from the rest of the brain. By keeping a small piece of the brain alive in a dish, researchers can directly observe and manipulate cells in a controlled environment. This approach maintains the natural arrangement and connections between brain cells, offering a more accurate representation of brain tissue than isolated cells in a culture.
Creating a Living Slice of Brain
Preparing a viable brain slice is a meticulous process that begins with the humane euthanasia of a laboratory animal, such as a mouse or rat. The brain is then rapidly extracted and submerged in an ice-cold, oxygenated solution. This cold temperature is important as it slows down metabolic activity, preserving the delicate neural tissue during the subsequent steps.
The brain is then mounted in a specialized instrument called a vibratome. This device uses a high-precision vibrating blade to cut the tissue into extremely thin sections, usually between 100 and 400 micrometers thick. The vibration allows the blade to slice through the tissue smoothly without crushing or tearing the cells, which would happen with a standard stationary blade.
Once cut, each slice is transferred to a chamber containing artificial cerebrospinal fluid (aCSF). This fluid is the slice’s life-support system, designed to mimic the environment of the living brain. It is rich in nutrients like glucose, balanced to a specific pH, and continuously bubbled with oxygen and carbon dioxide to keep the cells functional. The slices are allowed to recover in this solution for up to an hour before experiments begin.
Observing Brain Cells in Action
With a living brain slice prepared, scientists can use advanced techniques to record the activity of neurons. A primary method is electrophysiology, which measures the electrical signals that brain cells use to communicate. The patch-clamp method involves using a microscopic glass pipette, with a tip only a few micrometers wide, to form a tight seal with a single neuron’s membrane, allowing researchers to record its electrical activity.
This recording can reveal a neuron’s resting electrical state and how it fires action potentials, the fundamental units of neural information. Scientists can also use the pipette to inject small electrical currents into the cell to see how it responds. This allows for a detailed examination of how individual neurons process information and communicate through synaptic connections.
Another approach involves imaging techniques that make neural activity visible. Calcium imaging is a widely used method that uses fluorescent dyes that bind to calcium ions. When a neuron becomes active, calcium ions rush into the cell, causing the dye to light up. Using a microscope to detect these flashes allows scientists to visually track the activity of hundreds or thousands of neurons simultaneously.
Unlocking Secrets of Brain Function and Disease
Researchers use brain slices to understand normal brain function and the mechanisms of disease. The study of synaptic plasticity, the process by which connections between neurons strengthen or weaken, is a prime example. This mechanism is thought to underlie learning and memory, and brain slices have been instrumental in characterizing processes like Long-Term Potentiation (LTP), where synaptic connections become stronger after intense stimulation.
Brain slices are also invaluable for creating models of neurological and psychiatric disorders. For instance, researchers can induce seizure-like activity in a slice from the hippocampus to study the abnormal, synchronized firing of neurons that occurs during an epileptic seizure. This allows them to investigate how seizures start and spread and to test potential anti-epileptic drugs in a controlled setting.
Similarly, slices can be prepared from genetically modified animals that model human diseases like Alzheimer’s or Parkinson’s. This allows scientists to examine specific cellular changes associated with these conditions, such as the impact of amyloid plaques or the loss of dopamine-producing neurons. Researchers can then apply experimental drugs directly to the tissue to see if they can reverse or halt these pathological changes, providing a screening platform for new therapeutics.
The Role of Brain Slices in Modern Neuroscience
The brain slice technique serves as a bridge between studying the whole, living brain (in vivo) and analyzing isolated cells in a dish (in vitro). While in vivo studies provide the most complete picture of brain function, it is often difficult to control all variables or access individual neurons for detailed analysis.
On the other end of the spectrum, cell cultures offer a highly controlled environment where individual cells can be easily manipulated and studied. However, these cultures lack the brain’s complex, three-dimensional architecture and the intricate local circuits that define how neurons function.
The brain slice preparation offers a middle ground that preserves local, functional synaptic circuitry and the anatomical arrangement of different cell types. This allows for precise experimental control and direct application of drugs or electrical stimuli while maintaining a physiologically relevant context. Although the technique severs long-range connections, its ability to keep local networks intact makes it a valuable tool for dissecting brain function and disease.