Calcium imaging: A versatile tool to examine Huntington’s disease mechanisms and progression

Abstract

Huntington’s disease (HD) is a fatal, hereditary neurodegenerative disorder that causes chorea, cognitive deficits, and psychiatric symptoms. It is characterized by accumulation of mutant Htt protein, which primarily impacts striatal medium-sized spiny neurons (MSNs), as well as cortical pyramidal neurons (CPNs), causing synapse loss and eventually cell death. Perturbed Ca2+ homeostasis is believed to play a major role in HD, as altered Ca2+ homeostasis often precedes striatal dysfunction and manifestation of HD symptoms. In addition, dysregulation of Ca2+ can cause morphological and functional changes in MSNs and CPNs. Therefore, Ca2+ imaging techniques have the potential of visualizing changes in Ca2+ dynamics and neuronal activity in HD animal models. This minireview focuses on studies using diverse Ca2+ imaging techniques, including two-photon microscopy, fiber photometry, and miniscopes, in combination of Ca2+ indicators to monitor activity of neurons in HD models as the disease progresses. We then discuss the future applications of Ca2+ imaging to visualize disease mechanisms and alterations associated with HD, as well as studies showing how, as a proof-of-concept, Ca2+imaging using miniscopes in freely-behaving animals can help elucidate the differential role of direct and indirect pathway MSNs in HD symptoms.

NeuroActivityToolkit—Toolbox for Quantitative Analysis of Miniature Fluorescent Microscopy Data

“…Analyzing the burst-rate distribution could report the excitationinhibition balance, which is very important for proper brain functioning. The excitationinhibition disbalance has been observed in different neurodegenerative disorders [46,47], making its investigation utilizing the miniscope technique with subsequent data analysis via NeuroActivityToolkit a promising avenue for research. Furthermore, recording neuronal calcium dynamics with specific promoters for selective expression in the neuronal subtypes (CAMKII for most excitatory neurons [48,49] and mGAD65 [50] or others [51] for inhibitory neurons) might be a way to reveal the neuronal structure architecture of the complex networks in vivo in different regions of the brain.…”

Chorea: An unusual manifestation of endocrine diseases

“…Altered calcium homeostasis usually precedes striatal dysfunction. In addition, calcium dysregulation can cause morphological and functional changes in neurons (107). And sodium, as an important electrolyte for regulating osmotic pressure in the brain, can cause a series of neurological symptoms, such as chorea, due to blood-brain barrier alteration, mainly in the case of rapid correction of hyponatremia.…”