What are the implications for the existence of subthreshold ion channels, their localization profiles, and plasticity on local field potentials (LFPs)? Here, we assessed the role of hyperpolarizationactivated cyclic-nucleotide-gated (HCN) channels in altering hippocampal theta-frequency LFPs and the associated spike phase. We presented spatiotemporally randomized, balanced theta-modulated excitatory and inhibitory inputs to somatically aligned, morphologically realistic pyramidal neuron models spread across a cylindrical neuropil. We computed LFPs from seven electrode sites and found that the insertion of an experimentally constrained HCN-conductance gradient into these neurons introduced a location-dependent lead in the LFP phase without significantly altering its amplitude. Further, neurons fired action potentials at a specific theta phase of the LFP, and the insertion of HCN channels introduced large lags in this spike phase and a striking enhancement in neuronal spike-phase coherence. Importantly, graded changes in either HCN conductance or its half-maximal activation voltage resulted in graded changes in LFP and spike phases. Our conclusions on the impact of HCN channels on LFPs and spike phase were invariant to changes in neuropil size, to morphological heterogeneity, to excitatory or inhibitory synaptic scaling, and to shifts in the onset phase of inhibitory inputs. Finally, we selectively abolished the inductive lead in the impedance phase introduced by HCN channels without altering neuronal excitability and found that this inductive phase lead contributed significantly to changes in LFP and spike phase. Our results uncover specific roles for HCN channels and their plasticity in phase-coding schemas and in the formation and dynamic reconfiguration of neuronal cell assemblies.L ocal field potentials (LFPs) have been largely believed to be a reflection of the synaptic drive that impinges on a neuron. In recent experimental and modeling studies, there has been a lot of debate on the source and spatial extent of LFPs (1-9). However, most of these studies have used neurons with passive dendrites in their models and/or have largely focused on the contribution of spike-generating conductances to LFPs (7,8,10,11). Despite the widely acknowledged regulatory roles of subthreshold-activated ion channels and their somatodendritic gradients in the physiology and pathophysiology of synapses and neurons (12-17), the implications for their existence on LFPs and neuronal spike phase have surprisingly remained unexplored. This lacuna in LFP analysis is especially striking because local and widespread plasticity of these channels has been observed across several physiological and pathological conditions, translating to putative roles for these channels in neural coding, homeostasis, disease etiology and remedies, learning, and memory (16,(18)(19)(20)(21)(22)(23).In this study, we focus on the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that mediate the h current (I h ) in regulating LFPs and ...

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Delayed upregulation of the neuronal chloride extruder KCC2 underlies the progressive shift in GABA signaling polarity during development. Conversely, KCC2 is downregulated in a variety of neurological and psychiatric disorders often associated with cognitive impairment. Reduced KCC2 expression and function in mature networks may disrupt GABA signaling and promote anomalous network activities underlying these disorders. However, the causal link between KCC2 downregulation, altered brain rhythmogenesis and cognitive function remains elusive. Here, by combining behavioral exploration with in vivo electrophysiology we assessed the impact of chronic KCC2 silencing in mouse dorsal hippocampus and showed it compromises both spatial and contextual memory. This was associated with altered hippocampal rhythmogenesis and neuronal hyperexcitability, with increased CA1 pyramidal cell burst firing during non-REM sleep. Reducing neuronal excitability with terbinafine, a specific Task-3 leak potassium channel activator, occluded the impairment of contextual memory upon KCC2 silencing. Our results establish a causal relationship between KCC2 expression and cognitive performance and suggest that impaired rhythmopathies and neuronal hyperexcitability are central to the deficits caused by KCC2 silencing in the adult mouse brain.

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This paper describes key factors related to intelligent horizontal well completion systems and surveillance activities for a polymer field trial within a sandstone reservoir in the South of Oman. The existing field predominantly comprising of horizontal producer wells drilled and located at the crest of the reservoir to ensure optimum oil production rates via artificial lift techniques. Many wells have encountered early water breakthrough, resulting in large volumes of un-swept oil. Improved sweep efficiency, hence improved oil recovery is expected by polymer flooding using a horizontal well approach [1]. The polymer field trial location consists of: 4 horizontal producers each completed with wire wrap screens, blanks and external zonal isolation packers within the reservoir section for segmentation and isolation. Each producer has a downhole gauge for real-time pressure and temperature monitoring. Three horizontal smart injectors each consisting of 4 zones completed with 7 inch pre-drilled liners, blanks and external zonal isolation packers across the reservoir section for segmentation and zonal isolation. These injectors are internally completed with intelligent completion systems with remote access and control whereby each of the 4 zones consists of a mechanical retrievable packer for zonal isolation, on-off intelligent flow control valve with hydraulic multi-drop module system for conformance control, quartz pressure-temperature gauge, double ended pump down DTS system for real-time monitoring and internally lined GRE tubulars in order to prevent polymer degradation. Two horizontal observation wells each completed with GRE casings and predrilled liner joints for logging along with downhole gauges for real-time pressure-temperature monitoring. One vertical observation well completed with GRE casing and carbon steel casing below the oil water contact for surveillance purposes. A detailed surveillance plan for the current producers, injectors and observation wells is of utmost importance for pre and post injection data gathering in order to successfully evaluate key subsurface risks and uncertainties associated with the polymer flood technique. The field trial has been designed and executed with an optimum approach to ensure continuous real-time surveillance. This is facilitated by remote access and control thereby minimizing well interventions for surveillance activities for the duration of the trial.