Spatial information is encoded by location-dependent hippocampal place cell firing rates and sub-second, rhythmic entrainment of spike times. These rate and temporal codes have primarily been characterized in low-dimensional environments under limited cognitive demands; but how is coding configured in complex environments when individual place cells signal several locations, individual locations contribute to multiple routes and functional demands vary? Quantifying CA1 population dynamics of male rats during a decision-making task, here we show that the phase of individual place cells' spikes relative to the local theta rhythm shifts to differentiate activity in different place fields. Theta phase coding also disambiguates repeated visits to the same location during different routes, particularly preceding spatial decisions. Using unsupervised detection of cell assemblies alongside theoretical simulation, we show that integrating rate and phase coding mechanisms dynamically recruits units to different assemblies, generating spiking sequences that disambiguate episodes of experience and multiplexing spatial information with cognitive context. Russo et al. show that context-specific place cell assemblies support hippocampal integration of past experiences into future plans during goal-directed behavior and propose a biophysical mechanism behind the formation of goal dependent theta sequences.

Hippocampal sharp-wave ripples (SWRs) support the reactivation of memory representations, relaying information to neocortex during "offline" and sleep-dependent memory consolidation. While blockade of NMDA receptors (NMDAR) is known to affect both learning and subsequent consolidation, the specific contributions of NMDAR activation to SWR-associated activity remain unclear. Here, we combine biophysical modeling with in vivo local field potential (LFP) and unit recording to quantify changes in SWR dynamics following inactivation of NMDAR. In a biophysical model of CA3-CA1 SWR activity, we find that NMDAR removal leads to reduced SWR density, but spares SWR properties such as duration, cell recruitment and ripple frequency. These predictions are confirmed by experiments in which NMDAR-mediated transmission in rats was inhibited using three different NMDAR antagonists, while recording dorsal CA1 LFP. In the model, loss of NMDAR-mediated conductances also induced a reduction in the proportion of cell pairs that co-activate significantly above chance across multiple events. Again, this prediction is corroborated by dorsal CA1 single-unit recordings, where the NMDAR blocker ketamine disrupted correlated spiking during SWR. Our results are consistent with a framework in which NMDA receptors both promote activation of SWR events and organize SWR-associated spiking content. This suggests that, while SWR are short-lived events emerging in fast excitatory-inhibitory networks, slower network components including NMDAR-mediated currents contribute to ripple density and promote consistency in the spiking content across ripples, underpinning mechanisms for fine-tuning of memory consolidation processes.

The melodic contour of speech forms an important perceptual aspect of tonal and nontonal languages and an important limiting factor on the intelligibility of speech heard through a cochlear implant. Previous work exploring the neural correlates of speech comprehension identified a left-dominant pathway in the temporal lobes supporting the extraction of an intelligible linguistic message, whereas the right anterior temporal lobe showed an overall preference for signals clearly conveying dynamic pitch information [Johnsrude, I. S., Penhune, V. B., & Zatorre, R. J. Functional specificity in the right human auditory cortex for perceiving pitch direction. Brain, 123, 155-163, 2000; Scott, S. K., Blank, C. C., Rosen, S., & Wise, R. J. Identification of a pathway for intelligible speech in the left temporal lobe. Brain, 123, 2400-2406, 2000]. The current study combined modulations of overall intelligibility through vocoding and spectral inversion with a manipulation of pitch contour normal vs. falling to investigate the processing of spoken sentences in functional MRI. Our overall findings replicate and extend those of Scott et al. [Scott, S. K., Blank, C. C., Rosen, S., & Wise, R. J. Identification of a pathway for intelligible speech in the left temporal lobe. Brain, 123, 2400-2406, 2000], where greater sentence intelligibility was predominately associated with increased activity in the left STS, and the greatest response to normal sentence melody was found in right superior temporal gyrus. These data suggest a spatial distinction between brain areas associated with intelligibility and those involved in the processing of dynamic pitch information in speech. By including a set of complexity-matched unintelligible conditions created by spectral inversion, this is additionally the first study reporting a fully factorial exploration of spectrotemporal complexity and spectral inversion as they relate to the neural processing of speech intelligibility. Perhaps surprisingly, there was little evidence for an interaction between the two factors-we discuss the implications for the processing of sound and speech in the dorsolateral temporal lobes.

The discovery of cis‐regulatory elements is a challenging problem in bioinformatics, owing to distal locations and context‐specific roles of these elements in controlling gene regulation. Here we review the current bioinformatics methodologies and resources available for systematic discovery of cis‐acting regulatory elements and conserved transcription factor binding sites in the chick genome. In addition, we propose and make available, a novel workflow using computational tools that integrate CTCF analysis to predict putative insulator elements, enhancer prediction, and TFBS analysis. To demonstrate the usefulness of this computational workflow, we then use it to analyze the locus of the gene Sox2 whose developmental expression is known to be controlled by a complex array of cis‐acting regulatory elements. The workflow accurately predicts most of the experimentally verified elements along with some that have not yet been discovered. A web version of the CTCF tool, together with instructions for using the workflow can be accessed from http://toolshed.g2.bx.psu.edu/view/mkhan1980/ctcf_analysis. For local installation of the tool, relevant Perl scripts and instructions are provided in the directory named “code” in the supplementary materials. genesis 51:311–324. © 2013 Wiley Periodicals, Inc.