RT Journal Article SR Electronic T1 Long-Term Recordings Improve the Detection of Weak Excitatory–Excitatory Connections in Rat Prefrontal Cortex JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 5454 OP 5467 DO 10.1523/JNEUROSCI.4350-13.2014 VO 34 IS 16 A1 C. Daniela Schwindel A1 Karim Ali A1 Bruce L. McNaughton A1 Masami Tatsuno YR 2014 UL http://www.jneurosci.org/content/34/16/5454.abstract AB Characterization of synaptic connectivity is essential to understanding neural circuit dynamics. For extracellularly recorded spike trains, indirect evidence for connectivity can be inferred from short-latency peaks in the correlogram between two neurons. Despite their predominance in cortex, however, significant interactions between excitatory neurons (E) have been hard to detect because of their intrinsic weakness. By taking advantage of long duration recordings, up to 25 h, from rat prefrontal cortex, we found that 7.6% of the recorded pyramidal neurons are connected. This corresponds to ∼70% of the local E–E connection probability that has been reported by paired intracellular recordings (11.6%). This value is significantly higher than previous reports from extracellular recordings, but still a substantial underestimate. Our analysis showed that long recording times and strict significance thresholds are necessary to detect weak connections while avoiding false-positive results, but will likely still leave many excitatory connections undetected. In addition, we found that hyper-reciprocity of connections in prefrontal cortex that was shown previously by paired intracellular recordings was only present in short-distance, but not in long distance (∼300 micrometers or more) interactions. As hyper-reciprocity is restricted to local clusters, it might be a minicolumnar effect. Given the current surge of interest in very high-density neural spike recording (e.g., NIH BRAIN Project) it is of paramount importance that we have statistically reliable methods for estimating connectivity from cross-correlation analysis available. We provide an important step in this direction.