α4β2 antagonist  (Alomone Labs)

Journal: bioRxiv

Article Title: Co-activation of selective nicotinic acetylcholine receptor subtypes is required to reverse hippocampal network dysfunction and prevent fear memory loss in Alzheimer’s disease

doi: 10.1101/2024.07.08.602576

Figure Lengend Snippet: a) A simplified local inhibitory circuit in the hippocampus. PV+ interneurons mainly provide somatic inhibition to pyramidal excitatory neurons (Pyr), while SST+ interneurons provide dendritic inhibition. This contributes to hippocampal oscillations and cognitive function. α7-, α4β2-, and α3β4-nAChRs predominantly control nicotinic cholinergic signaling in PV-, SST-, and pyramidal cells, respectively. b) Aβ selectively inhibits α7- and α4β2-nAChRs in inhibitory cells, but not α3β4-nAChRs, in turn reduces inhibitory inputs to excitatory cells, which contributes to disruptions in hippocampal oscillations and consequent learning and memory in AD. c-d) Single stimulation of each nAChR subtype by PNU-282987 (PNU), an α7 agonist, or RJR-2403 Oxalate (RJR), an α4β2 agonist, is unable to reverse the Aβ-induced adverse effects on network activity and memory. e) Co-stimulation of α7- and α4β2-nAChRs sufficiently restores normal hippocampal oscillations and memory.

Article Snippet: The following nAChR antagonists were used in this study: α-Bungarotoxin (αBTx) (Alomone labs)), an α7 antagonist, Dihydro-β-erythroidine hydrobromide (DHβE) (Tocris Bioscience), an α4β2 antagonist, and α-Conotoxin AuIB (Alomone labs), an α3β4 antagonist.

Techniques: Inhibition, Control, Activity Assay

Journal: Journal of Neurophysiology

Article Title: A dominant role for the beta 4 nicotinic receptor subunit in nicotinic modulation of glomerular microcircuits in the mouse olfactory bulb

doi: 10.1152/jn.00925.2017

Figure Lengend Snippet: Effects of β-subunit knockouts on ACh/At-dependent increases in intracellular Ca2+ concentration in juxtaglomerular cells. A: example heat map depiction of 340/380 absorption ratio in a wild-type (WT) slice during 30-s baseline, 1-s ACh/At puff, and 30-s recovery periods. Baseline and recovery frames are averaged over 30 s, ACh/At frame averaged over 5 s from beginning of puff. Dashed line depicts the target glomerulus of the application pipette. Arrowheads in the ACh/At panel are used to highlight cells that show a higher Ca2+ signal than baseline. B: representative heat maps (normalized to baseline ratio) shown to demonstrate the gross effects of β-subunit knockouts on the ACh/At response. WT panel depicted was taken from the data set depicted in A. C: mean number of responsive juxtaglomerular cells from each slice used (*P < 0.05). D: net change in ACh/At-evoked calcium changes in juxtaglomerular cells from β2-knockouts (KOs) with the agonist alone (Control) or agonist in the presence of 10 µM conotoxin (CTx) AuIB. The β4-specific antagonist blocked ACh/At responses from these cells indicating that the responses in β2-KOs are primarily due to contributions from nicotinic acetylcholine receptors (nAChRs) containing the β4-subunit. E: average (± SE) trace of calcium transients from juxtaglomerular cells in β2-KOs in response to ACh/At. Control response (black); response in the presence of 10 µM CTx AuIB (red). F, left: mean ratio traces (± SE) from cells that showed positive Ca2+ signals in response to ACh/At application. Ca2+ signals were recorded at 1 Hz over 80 s; a 1-s ACh/At puff was applied at 30 s (shown in blue). Control, black; β2-KO, red; β4-KO, gray. Right: averaged traces normalized to the peaks showing faster decay of calcium transients from β2-KOs. G: average integrals of the calcium transient (red), peak response (green) and decay time constants (blue) of the ACh/At-driven calcium transients elicited from WT, β2-KOs, and β4-KOs.***P < 0.0002. ACh/At, 1 mM acetylcholine in the presence of 2 µM atropine.

Article Snippet: Conotoxin AuIB (CTx; Alomone Laboratories, Jerusalem, Israel) was used at 10 µM.

Techniques: Concentration Assay, Transferring