Neuroscience Research Tools and Techniques

Tools in Neuroscience Research

• Transcranial magnetic stimulation (TMS) is used to create "virtual lesions" and has potential therapeutic applications.
• Animal models include the Morris water maze, 5-choice serial reaction time task, conditioning (classical and operant), and the T-maze.
• The forced-swim test (FST) is a behavioral assay used to measure depression in rodents and evaluate antidepressant efficacy. However, interpretation can be challenging.
• Animal models are used because mammalian brain similarities exist, and animal cognition is sophisticated.
• Potential drug routes include intramuscular (IM), intravenous (IV), subcutaneous (SC), intraperitoneal (IP), and intraventricular.
• Multiple drug doses, often starting with saline, are crucial for effective studies, along with control groups. The within-subjects design is commonly used to enhance these studies.

Invasive Electrical Recording Methods

• Four invasive electrophysiological methods include intracellular unit recording, extracellular unit recording, multiple-unit recording, and invasive EEG recording.

Stereotaxic Surgery

• Stereotaxic surgery, used for lesions, optogenetics, and electrode implantation, employs a stereotaxic atlas and instrument.
• Precise placement is enabled by the stereotaxic atlas and instrument, including the use of bregma as a reference point.

Lesion Methods

• Chemical lesions, such as quinolinic acid and ibotenic acid, are excitotoxic.
• Selective chemical lesions include 6-hydroxydopamine (6-OHDA) and 5,7-dihydroxytriptamine (5,7-DHT).
• Reversible lesions can be achieved using cannulae and methods like baclofen + muscimol, which are beneficial because of the within-subjects design.
• Different lesion approaches (unilateral, bilateral, or contralateral) in studies should be carefully considered.

Optogenetics

• Optogenetics introduces light-gated ion channels, such as channelrhodopsins.
• System-specific transcription factors can be used.
• Optogenetics can be used for recording/mapping and manipulation.

Reminder: Stains are Cool

• Golgi stain, Nissl stain/cresyl violet stain, and fiber stains are useful tools.
• Luxol-fast blue (LFB) and toluidine blue are specific fiber stains.
• Green fluorescent protein (GFP) derivatives (e.g., YFP, BFP) can be introduced into living cells for imaging studies.

Neuroimaging: Structural and Functional

• Static (structural) neuroimaging includes computerized axial tomography (CAT/CT), magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI).
• Dynamic (functional) neuroimaging includes positron emission tomography (PET), functional MRI (fMRI), and resting-state functional connectivity MRI (rsfcMRI).

X-Ray

• X-ray imaging uses an X-ray tube, beam, and film or detectors to produce images.

Computed Tomography (CT)

• CT involves a tube and detector for imaging.
• Early CT was limited by its algorithm quality but useful for stroke studies.

Magnetic Resonance Imaging (MRI)

• MRI, utilizing the rotation of hydrogen atoms' protons in a magnetic field, provides structural brain imaging.
• The technology produces detailed images based on aligning protons in a magnetic field.

Diffusion Tensor Imaging (DTI)

• DTI is a variant of MRI that focuses on water molecule movement to produce images of brain tracts.

Positron Emission Tomography (PET)

• PET uses radiolabeled molecules (e.g., cocaine) to visualize brain activity, often indirectly.
• This method is less common now due to cost and time constraints, but provides valuable insight into targeted brain systems.
• PET uses paired image subtraction (as fMRI) but with its own unique limitations.

Functional MRI (fMRI)

• fMRI measures blood oxygenation changes associated with neuronal activity. This is called the BOLD response.
• fMRI, like PET, often employs paired image subtraction techniques to analyze data. Event-related fMRI designs are now common for reducing some of these biases.
• fMRI has some limitations that must be considered when interpreting results. These include issues like spatial averaging, spatial and temporal resolution, and focusing on increases in activity. The default mode network (DMN) is more active during rest/passive states than task states in some regions. These methods are often not without confounding issues that influence the interpretation of data.