Imaging pathological activities of human brain tissue in organotypic culture

Abstract

Characteristic morphology and region-specific neuronal activities are maintained in organotypic culture of tissue from patients diagnosed with mesial temporal lobe epilepsy, cortical dysplasia and cortical glioblastoma. Viral vector techniques permit expression of probes for long-term measurements of multi-cellular activity and intra-cellular signaling.

Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds

“…Transgenes such as GCaMP6 (a Ca 2? indicator), carried by AAV or LV vectors and applied during culture preparation, can be stably expressed at 2 weeks-3 weeks, allowing simultaneous electrical and optical recordings of neuronal Ca 2? transients [43]. The findings described above show that, under suitable circumstances, resected human brain slices in culture can show long-term survival and enable experimental approaches such as transgene expression.…”

“…Extracellular population recording has revealed tonic and rhythmic network activity in human brain slices [41]. Furthermore, in hippocampal and temporal lobe slices, characteristic epileptiform activity can be maintained and recorded in vitro [42,43]. The in vitro spontaneous interictal-like activity recorded in the subiculum of human acute temporal lobe slice cultures appears to resemble intracranial EEG recordings from the same patient with temporal lobe epilepsy [44].…”

“…That study shows that optogenetics can become a practical tool to explore synaptic connectivity and neuronal networks in human brain tissue cultures. Recent work has explored the optimal conditions for long-term cultures of human brain slices for up to one month [43]. Studies have shown that the regional organization and neuronal physiology and morphology of the dentate gyrus, CA2/3, subiculum, and cortex surgically excised from the human temporal lobe and peri-tumoral or dysplastic cortex maintained for 5 weeks-6 weeks using a new defined culture medium are similar to acute slices, as indicated by immunohistochemistry, whole cell recording, and spontaneous synaptic events [43].…”

“…Recent work has explored the optimal conditions for long-term cultures of human brain slices for up to one month [43]. Studies have shown that the regional organization and neuronal physiology and morphology of the dentate gyrus, CA2/3, subiculum, and cortex surgically excised from the human temporal lobe and peri-tumoral or dysplastic cortex maintained for 5 weeks-6 weeks using a new defined culture medium are similar to acute slices, as indicated by immunohistochemistry, whole cell recording, and spontaneous synaptic events [43]. In contrast, some studies [25,27] have reported the emergence of reactive glial cells and concurrent degeneration of neurons in cultured resected brain tissue.…”

The Beauty and the Dish: Brain Organoids Go Active

“…They can be combined with organotypic cultures of cortical surgical samples given recent advances in protocols allowing for optimized transduction of transgenes and viral vector strategies. [16][17][18] Together, these 2 in vitro tools may transform the study of the human brain ex vivo in a more personalized way (Figure 1). Oscillations not only represent the basic functional mode of the brain but they are essential for a proper construction.…”