Physical principles for scalable neural recording.

Simultaneously measuring the activities of all neurons in a mammalian brain at millisecond resolution is a challenge beyond the limits of existing techniques in neuroscience. Entirely new approaches may be required, motivating an analysis of the fundamental physical constraints on the problem. We outline the physical principles governing brain activity mapping using optical, electrical, magnetic resonance, and molecular modalities of neural recording. Focusing on the mouse brain, we analyze the scalability of each method, concentrating on the limitations imposed by spatiotemporal resolution, energy dissipation, and volume displacement. Based on this analysis, all existing approaches require orders of magnitude improvement in key parameters. Electrical recording is limited by the low multiplexing capacity of electrodes and their lack of intrinsic spatial resolution, optical methods are constrained by the scattering of visible light in brain tissue, magnetic resonance is hindered by the diffusion and relaxation timescales of water protons, and the implementation of molecular recording is complicated by the stochastic kinetics of enzymes. Understanding the physical limits of brain activity mapping may provide insight into opportunities for novel solutions. For example, unconventional methods for delivering electrodes may enable unprecedented numbers of recording sites, embedded optical devices could allow optical detectors to be placed within a few scattering lengths of the measured neurons, and new classes of molecularly engineered sensors might obviate cumbersome hardware architectures. We also study the physics of powering and communicating with microscale devices embedded in brain tissue and find that, while radio-frequency electromagnetic data transmission suffers from a severe power-bandwidth tradeoff, communication via infrared light or ultrasound may allow high data rates due to the possibility of spatial multiplexing. The use of embedded local recording and wireless data transmission would only be viable, however, given major improvements to the power efficiency of microelectronic devices.

Inhibition of Dugbe nairovirus replication by human MxA protein.

Sensitivity to the interferon-induced protein, MxA, has previously been demonstrated for viruses belonging to the Orthobunyavirus, Hantavirus and Phlebovirus genera of the Bunyaviridae family. We have extended these findings to a member of the fourth and remaining genus containing viruses that infect man and other animals, the nairovirus Dugbe virus (DUGV). Indirect immunofluorescence experiments using VA9 cells (Vero cells permanently transfected with MxA cDNA) revealed strongly reduced DUGV antigen expression, suggesting that MxA inhibited DUGV replication. Western and Northern blot analyses showed significantly lower DUGV nucleocapsid (N) protein expression and DUGV genomic RNA, respectively, in the presence of MxA. Viral titres were also reduced by more than two orders of magnitude in VA9 cells compared with control VN36 cells. This finding may have application to nairovirus therapeutics.

Dugbe nairovirus S segment: correction of published sequence and comparison of five isolates.

The sequence of the S (small) RNA segment of the ArD 44313 isolate of Dugbe nairovirus (DUG) has been redetermined, and a number of apparent errors in the previously reported sequence (V. K. Ward, A. C. Marriott, A. A. El-Ghorr, and P. A. Nuttall, 1990, Virology 175, 518-524) were revealed. Our results indicate that the S RNA is 1716 nucleotides (nt) in length and contains one large open reading frame spanning 1449 nt. This can encode a 483 amino acid polypeptide, M(r) 53.9 kDa, corresponding to the viral nucleocapsid protein N. The DUG N protein is thus similar in length to the N proteins of Hazara (HAZ) and Crimean-Congo haemorrhagic fever (CCHF) nairoviruses, which are 485 and 482 amino acids in length, respectively. S segment RNA sequences were also determined for DUG isolates IbAr 1792, IbH 11480, ArD 16095, and KT 281/75; only the KT 281/75 sequence differed markedly from that of ArD 44313. Phylogenetic trees were constructed for these nairovirus S segment sequences.