Genetically encoded sensors for measuring histamine release both in vitro and in vivo

Histamine originating from the BNST modulates corticostriatal synaptic transmission during early postnatal development

“…To first confirm that the sensor is responsive to histamine these HA1h GRAB HA sensor-expressing SPNs were imaged for brief periods of time (1-2 seconds) while being illuminated with a wide-field 473 nm LED both before and during superfusion with histamine (10 µM). This revealed that indeed this method of expression in striatal neurons led to functional GRAB HA sensors which exhibited a significant increase in fluorescence in the presence of histamine (0.30 ± 0.09, 11F / F 0 , p=0.049, one sample t -test, n = 4 cells, 3 mice) comparable to that seen using other methods of delivery of the sensor ( Dong et al, 2023 ) ( Figure 5G ).…”

“…On average we find that electrical stimulation led to a significant increase of both dopamine (45.3 ± 5.6 nM, paired t -test, p=0.0002) and histamine (178.5 ± 57.7 nM, paired t -test, p=0.009) which peaked at respectively 5.6 ± 0.07 s and 7.0 ± 0.2 s after stimulation (p=0.0016, paired t -test) with histamine lingering for significantly longer in the tissue (dopamine: 6.6 ± 0.4 s and histamine: 18.7 ± 3.7 s, p=0.019, paired t -test, n=6 brain sections from 3 mice, Figure 5C ). Secondly, to further confirm that stimulation of ovBNST can generate a significant histamine transient in the striatum recently developed GRAB HA fluorescent sensors were used ( Dong et al, 2023 ). Here plasmid DNA containing the HA1h variant of the GRAB HA sensor was injected into the ventricles of developing mouse embryos and delivered to neuronal progenitors in the embryonic LGE using in utero electroporation ( van Heusden et al, 2021 ).…”

“…Here plasmid DNA containing the HA1h variant of the GRAB HA sensor was injected into the ventricles of developing mouse embryos and delivered to neuronal progenitors in the embryonic LGE using in utero electroporation ( van Heusden et al, 2021 ). This allowed for the labelling of postnatal striatal SPNs with the HA1h GRAB HA sensor which is endogenously fluorescent ( Dong et al, 2023 ) ( Figure 5E ). Acute coronal striatal sections were made from electroporated pups at P9-15 of age and sections were selected that contained the ovBNST as well as SPNs located near the ovBNST expressing the HA1h GRAB HA sensor ( Figure 5E, F ).…”

“…As histamine is thought to be released all along the axons coming from histaminergic neurons in the TMN this suggests that densely innervated regions can form a source of physiological histamine. Indeed, using trains of electrical stimulation of the ovBNST and using recently developed GRAB HA sensors expressed in striatal SPNs we show that SPNs located hundreds of micrometers away from the ovBNST can detect significant levels of histamine ( Dong et al, 2023 ). Similarly, FCV recordings in striatum made at similar distances showed that electrical stimulation of the ovBNST induced a prolonged histamine transient ranging in the tens of seconds as well as an initial fast dopamine transient.…”

“…Histamine concentrations in the brain have classically been investigated using techniques such as microdialysis and high-performance liquid chromatography which have suggested that extracellular histamine can be detected for long periods of time after electrically evoked release in adult rodents and is detectable for minutes (Cumming, 1991a). More recent techniques based on fluorescent sensors also support this extended life-time of extracellular histamine (Dong et al, 2023). This contrasts with many other monoamines including dopamine, which has a half-life ranging in the hundreds of milliseconds and highly spatially restricted actions Salinas et al, 2016;Sulzer et al, 2016;Hamid et al, 2021).…”