nAChRs in β4 knockout (KO) mice were reduced to < 15% of controls and no longer contained the α5 subunit. Compound action potentials, recorded from the postganglionic (internal carotid) nerve and induced by preganglionic nerve stimulation, did not differ between α5β4 KO and WT mice, suggesting that the reduced number of receptors in the KO mice did not impair transganglionic transmission. Deletions of α5 or β2 did not affect the overall number of receptors and we found no evidence that the two subunits substitute for each other. In addition, dual KOs allowed us to study the functional properties of distinct α3β4 and α3β2 receptors that have previously only
been investigated in heterologous expression systems. The two receptors strikingly differed in the decay of macroscopic currents, the efficacy of cytisine, and their responses to the α-conotoxins Talazoparib order AuIB and MII. Our data, based on biochemical and functional experiments and several mouse KO models, clarify and significantly extend previous RO4929097 supplier observations on the function of nAChRs in heterologous systems and the SCG. “
“Advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and
schizophrenia. A previous study in mice suggested that the offspring of aged sires have altered locomotion and avoidance learning. The aim of the current study was to conduct a comprehensive behavioural screen in adult offspring of mice of APA. We also examined brain morphology in neonate and adult mice. The adult offspring of 12- to18-month-old (APA) and 4-month-old (control) male C57BL/6J
mice underwent a behavioural test battery comprising tests for locomotion, anxiety, exploration, social behaviour, learned helplessness and sensorimotor gating. The brains of these mice were collected Dapagliflozin at 3 months and imaged ex vivo using a 16.4T MRI scanner to assess gross neuroanatomy. Neuroanatomy was also examined at birth in a separate cohort of animals. Overall, the APA mouse model was associated with subtle behavioural changes and altered cortical morphology. The behavioural phenotype of female APA mice included increased anxiety-related behaviour, increased exploration and decreased learned helplessness compared to control females. Male APA mice had thinner cortices at birth and increased cortical volume as adults. This animal model may assist in exploring the mechanism of action linking APA with disorders such as schizophrenia and autism. “
“Tropomyosin-related kinase (Trk) receptors modulate neuronal structure and function both during development and in the mature nervous system. Interestingly, TrkB and TrkC are expressed as full-length and as truncated splice variants. The cellular function of the kinase-lacking isoforms remains so far unclear. We investigated the role of the truncated receptor TrkB.