An allosteric potentiator of M4 mAChR modulates hippocampal synaptic transmission.

Muscarinic acetylcholine receptors (mAChRs) provide viable targets for the treatment of multiple central nervous system disorders. We have used cheminformatics and medicinal chemistry to develop new, highly selective M₄ allosteric potentiators. VU10010, the lead compound, potentiates the M₄ response to acetylcholine 47-fold while having no activity at other mAChR subtypes. This compound binds to an allosteric site on the receptor and increases affinity for acetylcholine and coupling to G proteins. Whole-cell patch clamp recordings revealed that selective potentiation of M₄ with VU10010 increases carbachol-induced depression of transmission at excitatory but not inhibitory synapses in the hippocampus. The effect was not mimicked by an inactive analog of VU10010 and was absent in M₄ knockout mice. Selective regulation of excitatory transmission by M₄ suggests that targeting of individual mAChR subtypes could be used to differentially regulate specific aspects of mAChR modulation of function in this important forebrain structure.

Spectrally efficient cooperative diversity protocol for uplink wireless transmission

A spectrally efficient cooperative protocol for uplink wireless transmission in a centralised communication system is proposed, where each of the N users play the relaying and source roles simultaneously by using superposition (SP) modulation. The probability density function of the mutual information between SP-modulated transmitted and received signals of the cooperative uplink channels is derived. Using the high-signal-to-noise ratio (SNR) approximation of this density function, the outage probability formula of the system as well as its easily computable tight upper and lower bounds are obtained and these formulas are evaluated numerically. Numerical results show that the proposed strategy can achieve around 3 dB performance gain over comparable schemes. Furthermore, the multiplexing and diversity tradeoff formula is derived to illustrate the optimal performance of the proposed protocol, which also confirms that the SP relaying transmission does not cause any loss of data rate. Moreover, performance characterisation in terms of ergodic and outage capacities are studied and numerical results show that the proposed scheme can achieve significantly larger outage capacity than direct transmission, which is similar to other cooperative schemes. The superiority of the proposed strategy is demonstrated by the fact that it can maintain almost the same ergodic capacity as the direct transmission, whereas the ergodic capacity of other cooperative schemes would be much worse.

Cooperative transmission protocol with full diversity and iterative detection

The authors propose a three-node full diversity cooperative protocol, which allows the retransmission of all symbols. By allowing multiple nodes to transmit simultaneously, relaying transmission only consumes limited bandwidth resource. To facilitate the performance analysis of the proposed cooperative protocol, the lower and upper bounds of the outage probability are first developed, and then the high signal-to-noise ratio behaviour is studied. Our analytical results show that the proposed strategy can achieve full diversity. To achieve the performance gain promised by the cooperative diversity, at the relays decode-and-forward strategy is adopted and an iterative soft-interference-cancellation minimum mean-squared error equaliser is developed. The simulation results compare the bit-error-rate performance of the proposed protocol with the non-cooperative scheme and the scheme presented by Azarian et al. ( 2005).