Viral vector-based tools advance knowledge of basal ganglia anatomy and physiology

Abstract

Viral vectors were originally developed to deliver genes into host cells for therapeutic potential. However, viral vector use in neuroscience research has increased because they enhance interpretation of the anatomy and physiology of brain circuits compared with conventional tract tracing or electrical stimulation techniques. Viral vectors enable neuronal or glial subpopulations to be labeled or stimulated, which can be spatially restricted to a single target nucleus or pathway. Here we review the use of viral vectors to examine the structure and function of motor and limbic basal ganglia (BG) networks in normal and pathological states. We outline the use of viral vectors, particularly lentivirus and adeno-associated virus, in circuit tracing, optogenetic stimulation, and designer drug stimulation experiments. Key studies that have used viral vectors to trace and image pathways and connectivity at gross or ultrastructural levels are reviewed. We explain how optogenetic stimulation and designer drugs used to modulate a distinct pathway and neuronal subpopulation have enhanced our mechanistic understanding of BG function in health and pathophysiology in disease. Finally, we outline how viral vector technology may be applied to neurological and psychiatric conditions to offer new treatments with enhanced outcomes for patients.

Optogenetic stimulation: Understanding memory and treating deficits

“…This has important specificity and functional implications because longer gene sequences and multiple genes can be inserted, which will be discussed below. Conversely, AAV particles are much smaller (20 nm), permitting it to diffuse further and enabling larger nuclei and brain regions, such as cortical areas, to be transduced for a given volume (Sizemore, Seeger‐Armbruster, Hughes, & Parr‐Brownlie, ). For AAV9 and AAVrh10, an additional advantage is that they can cross the blood brain barrier, so that brain neurons can be transduced when the viral vector is administered in the periphery (Sizemore et al, ).…”

“…Conversely, AAV particles are much smaller (20 nm), permitting it to diffuse further and enabling larger nuclei and brain regions, such as cortical areas, to be transduced for a given volume (Sizemore, Seeger‐Armbruster, Hughes, & Parr‐Brownlie, ). For AAV9 and AAVrh10, an additional advantage is that they can cross the blood brain barrier, so that brain neurons can be transduced when the viral vector is administered in the periphery (Sizemore et al, ). However, the genomic capacity for AAVs is only 4 kb (Rein & Deussing, ), which restricts the use of large, complex and sometimes multiple genes.…”

Optogenetic approaches for dissecting neuromodulation and GPCR signaling in neural circuits

“…These tools are expressed either virally or through transgenic animal approaches. Viral delivery is the most widely used route for expressing transgenes [124]. Viral delivery requires less commitment of resources needed to generate and maintain a genetic line.…”

“…Additionally, viral expression is limited to the site of infection, increasing spatial resolution. Adeno-associated viruses (AAV) and lentiviruses are most commonly used [21**,27**,124]. Preference of viral vector can depend on desired specificity of expression.…”

Irrational lighting as a health risk occurring in the Arctic

“…В работах R.J. Sizemore и др. [22], В. Шевченко [23] говорится, что классическими оптогенетическими инструментами являются белки галородопсин, археародопсин и канальный родопсин (рис. 9).…”