Here, we employ a WKB theory and directly treat the underlying Markov chain (formulated as a birth-death process) obeyed

by the allele frequency (whose dynamics is prescribed by the Moran model). Importantly, this approach S63845 order allows to accurately account for effects of large fluctuations. After a general description of the theory, we focus on the case of a deleterious mutant allele (i.e. s > 0) and discuss three situations: when the mutant is (i) completely dominant (s = h); (ii) completely recessive (h = 0), and (iii) semi-dominant (h = s/2). Our theoretical predictions for the mean fixation time and the quasi-stationary distribution of the mutant population in the coexistence state, are shown to be in excellent agreement PRI-724 price with numerical simulations. Furthermore, when s is finite, we demonstrate that our results are superior to those of the diffusion

theory, while the latter is shown to be an accurate approximation only when N(e)s(2) << 1, where N-e is the effective population size. (c) 2011 Elsevier Ltd. All rights reserved.”
“These experiments determined the mesolimbic modulation of cortical cholinergic transmission in a neurodevelopmental model of schizophrenia. Mesolimbic-cholinergic abnormalities are hypothesized to contribute to the cognitive deficits seen in schizophrenia. Stimulation of NMDA receptors in nucleus accumbens (NAC) increases acetylcholine (ACh) release in the prefrontal cortex (PFC), a mechanism recently demonstrated to contribute to the control of attentional performance. We determined the ability of intra-NAC administration of NMDA to increase prefrontal ACh levels in adult rats that had received bilateral infusions of tetrodotoxin (TTX) to transiently interrupt impulse flow in the ventral hippocampus (VH) during development.

Rats received infusions of TTX or saline on postnatal day 7 (PD7) or day 32 (PD32), and the effects of NAC NMDA receptor stimulation on prefrontal cholinergic neurotransmission over were assessed in adulthood. In animals treated as controls on PD7, NMDA increased prefrontal ACh levels by 121% above baseline. In contrast, PD7 infusions of TTX into the VH abolished the ability of NAC NMDA to activate prefrontal cholinergic neurotransmission (7% increase). In animals that received TTX infusions on PD32, NMDA-evoked cholinergic activity did not differ from controls, indicating a restricted, neonatal critical period during which VH TTX impacts the organization of mesolimbic-basal forebrain-cortical circuitry. Importantly, the failure of NAC NMDA to evoke cholinergic activity in rats treated with TTX on PD7 did not reflect a reduced excitability of corticopetal cholinergic neurons because administration of amphetamine produced similar elevations of prefrontal ACh levels in PD7 TTX and PD7 control animals.