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Recent technical advancements in neural engineering allow for precise recording and control of neural circuits simultaneously, opening up new opportunities for closed-loop neural control. In this work, a rapid spike sorting system was developed based on template matching to rapidly calculate instantaneous firing rates for each neuron in a multi-unit extracellular recording setting. Cluster templates were first generated by a desktop computer using a non-parameter spike sorting algorithm (Super-paramagnetic clustering) and then transferred to a field-programmable gate array digital circuit for rapid sorting through template matching. Two different matching techniques-Euclidean distance (ED) and correlational matching (CM)-were compared for the accuracy of sorting and the performance of calculating firing rates. The performance of the system was first verified using publicly available artificial data and was further confirmed with pre-recorded neural spikes from an anesthetized Mongolian gerbil. Real-time recording and sorting from an awake mouse were also conducted to confirm the system performance in a typical behavioral neuroscience experimental setting. Experimental results indicated that high sorting accuracies were achieved for both template-matching methods, but CM can better handle spikes with non-Gaussian spike distributions, making it more robust for in vivo recording. The technique was also compared to several other off-line spike sorting algorithms and the results indicated that the sorting accuracy is comparable but sorting time is significantly shorter than these other techniques. A low sorting latency of under 2 ms and a maximum spike sorting rate of 941 spikes/second have been achieved with our hybrid hardware/software system. The low sorting latency and fast sorting rate allow future system developments of neural circuit modulation through analyzing neural activities in real-time.

Objective: The ability to record and to control action potential firing in neuronal circuits is critical to understand how the brain functions. The objective of this study is to develop a monolithic integrated circuit (IC) to record action potentials and simultaneously control action potential firing using optogenetics. Methods: A low-noise and high input impedance (or low input capacitance) neural recording amplifier is combined with a high current laser/light-emitting diode (LED) driver in a single IC. Results: The low input capacitance of the amplifier (9.7 pF) was achieved by adding a dedicated unity gain stage optimized for high impedance metal electrodes. The input referred noise of the amplifier is $\text{4.57}\,{\mu} {\rm{V}}_{{\rm{rms}}}$ , which is lower than the estimated thermal noise of the metal electrode. Thus, the action potentials originating from a single neuron can be recorded with a signal-to-noise ratio of at least 6.6. The LED/laser current driver delivers a maximum current of 330 mA, which is adequate for optogenetic control. The functionality of the IC was tested with an anesthetized Mongolian gerbil and auditory stimulated action potentials were recorded from the inferior colliculus. Spontaneous firings of fifth (trigeminal) nerve fibers were also inhibited using the optogenetic protein Halorhodopsin. Moreover, a noise model of the system was derived to guide the design. Significance: A single IC to measure and control action potentials using optogenetic proteins is realized so that more complicated behavioral neuroscience research and the translational neural disorder treatments become possible in the future.

Emotional changes, impairment of object recognition, and neuroinflammation are seen in Parkinson's disease with dementia (PDD). Here, we show that bilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the rat substantia nigra pars compacta (SNc) of Wistar rats caused degeneration of nigrostriatal dopaminergic neurons, microglial activation in the SNc and hippocampus, and cell loss in the hippocampal CA1 area. With regard to behavior, an increase in anxiety-like behavior and impairment of object recognition were observed during the fourth week after MPTP lesioning. The behavioral changes were not caused by motor impairment, since the rats had already recovered from MPTP-induced catalepsy before the tests were performed. These findings show that MPTP-induced neuroinflammation and its consequences, for example, microglial activation and cell loss in the hippocampus, may be involved in dopaminergic degeneration-related behavioral deficits and suggest that, in addition to the dopaminergic system, the limbic system may also participate in the pathophysiology of PDD. MPTP-lesioned rats are therefore proposed as a useful tool for assessing the ability of pharmacological agents to prevent recognition deficits in PDD.

Human telomeric repeat binding factor 1(TRF1) contains one Myb-type DNA-binding repeat and an amino-terminal acidic domain. It can bind to the duplex array of TTAGGG repeats at chromosome ends and is shown to be important in preserving genomic stability, maintaining cell proliferative capacity, and blocking the activation of DNA-damage cell cycle checkpoints. Interestingly, the double strand DNA breaks sensor ATM interacts with and phosphorylates Pin2/TRF1 and inhibits its function after DNA damage. Are there some proteins else that can interact with TRF1 and influence its function? In order to analysis the interaction between TRF1 and other proteins, we must prepare the antiserum that can recognize the endogenous TRF1 of cell lysates. TRF1 cDNA was amplified using cDNA Library of HeLa cell by PCR and cloned into pUCm-T vector. Sequence analysis reveals identity to the GenBank report. The TRF1 cDNA was subcloned into expression vector pET-28c(+) and expressed in E. coli as a fusion protein of 65 kD. The recombinant TRF1 can express in the supernatant (about 12.3% in total protein) on the induction of 0.5 mmol/L IPTG at 37 degrees C for 3 hours. Western-blot analysis showed the recombinant protein can react with TRF1 polyclonal antibody sc-6165 (from Santa Cruz Company). His6-TRF1 was purified by Ni(2+) -NTA resin affinity chromatography made by ourselves and showed to be homogeneity in SDS-PAGE. Rabbits were immunized for four times to prepare polyclonal antibody. The unpurified antiserum can recognize the overexpressed TRF1 with myc-tag and the endogenous Pin2/TRF1 of cell lysate by Western-blot at 1:1000 dilution. At 1:400 dilution, the antiserum can interact with endogenous TRF1 by Immunofluorescence cell staining analysis. The endogenous TRF1 in different cell lines, such as HepG2, 803, MCF7 and HeLa, locates in the nucleus. The soluble expression TRF1 and preparation of its antibody lay the foundation to study it further.