Linking Cellular Mechanisms to Behavior: Entorhinal Persistent Spiking and Membrane Potential Oscillations May Underlie Path Integration, Grid Cell Firing, and Episodic Memory

The entorhinal cortex plays an important role in spatial memory and episodic memory functions. These functions may result from cellular mechanisms for integration of the afferent input to entorhinal cortex. This article reviews physiological data on persistent spiking and membrane potential oscillations in entorhinal cortex then presents models showing how both these cellular mechanisms could contribute to properties observed during unit recording, including grid cell firing, and how they could underlie behavioural functions including path integration. The interaction of oscillations and persistent firing could contribute to encoding and retrieval of trajectories through space and time as a mechanism relevant to episodic memory.Silvio O. Conte Center (NIMH MH71702, MH60450); National Institute of Mental Health Research (MH60013, MH61492); National Science Foundation (SLC SBE 0354378); National Institute of Drug Abuse (DA16454)

Parallel and convergent processing in grid cell, head-direction cell, boundary cell, and place cell networks.

The brain is able to construct internal representations that correspond to external spatial coordinates. Such brain maps of the external spatial topography may support a number of cognitive functions, including navigation and memory. The neuronal building block of brain maps are place cells, which are found throughout the hippocampus of rodents and, in a lower proportion, primates. Place cells typically fire in one or few restricted areas of space, and each area where a cell fires can range, along the dorsoventral axis of the hippocampus, from 30 cm to at least several meters. The sensory processing streams that give rise to hippocampal place cells are not fully understood, but substantial progress has been made in characterizing the entorhinal cortex, which is the gateway between neocortical areas and the hippocampus. Entorhinal neurons have diverse spatial firing characteristics, and the different entorhinal cell types converge in the hippocampus to give rise to a single, spatially modulated cell type-the place cell. We therefore suggest that parallel information processing in different classes of cells-as is typically observed at lower levels of sensory processing-continues up into higher level association cortices, including those that provide the inputs to hippocampus. WIREs Cogn Sci 2014, 5:207-219. doi: 10.1002/wcs.1272 Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website

Segregation of cortical head direction cell assemblies on alternating theta cycles

High-level cortical systems for spatial navigation, including entorhinal grid cells, critically depend on input from the head direction system. We examined spiking rhythms and modes of synchrony between neurons participating in head direction networks for evidence of internal processing, independent of direct sensory drive, which may be important for grid cell function. We found that head direction networks of rats were segregated into at least two populations of neurons firing on alternate theta cycles (theta cycle skipping) with fixed synchronous or anti-synchronous relationships. Pairs of anti-synchronous theta cycle skipping neurons exhibited larger differences in head direction tuning, with a minimum difference of 40 degrees of head direction. Septal inactivation preserved the head direction signal, but eliminated theta cycle skipping of head direction cells and grid cell spatial periodicity. We propose that internal mechanisms underlying cycle skipping in head direction networks may be critical for downstream spatial computation by grid cells.We kindly thank S. Gillet, J. Hinman, E. Newman and L. Ewell for their invaluable consultations and comments on previous versions of this manuscript, as well as M. Connerney, S. Eriksson, C. Libby and T. Ware for technical assistance and behavioral training. This work was supported by grants from the National Institute of Mental Health (R01 MH60013 and MH61492) and the Office of Naval Research Multidisciplinary University Research Initiative (N00014-10-1-0936). (R01 MH60013 - National Institute of Mental Health; MH61492 - National Institute of Mental Health; N00014-10-1-0936 - Office of Naval Research Multidisciplinary University Research Initiative)Accepted manuscrip

A Model Combining Oscillations and Attractor Dynamics for Generation of Grid Cell Firing

Different models have been able to account for different features of the data on grid cell firing properties, including the relationship of grid cells to cellular properties and network oscillations. This paper describes a model that combines elements of two major classes of models of grid cells: models using interactions of oscillations and models using attractor dynamics. This model includes a population of units with oscillatory input representing input from the medial septum. These units are termed heading angle cells because their connectivity depends upon heading angle in the environment as well as the spatial phase coded by the cell. These cells project to a population of grid cells. The sum of the heading angle input results in standing waves of circularly symmetric input to the grid cell population. Feedback from the grid cell population increases the activity of subsets of the heading angle cells, resulting in the network settling into activity patterns that resemble the patterns of firing fields in a population of grid cells. The properties of heading angle cells firing as conjunctive grid-by-head-direction cells can shift the grid cell firing according to movement velocity. The pattern of interaction of oscillations requires use of separate populations that fire on alternate cycles of the net theta rhythmic input to grid cells

Sources of the spatial code within the hippocampus

Neurons in the hippocampus are thought to provide information on an animal's location within its environment. Input to the hippocampus comes via afferents from the entorhinal cortex, which are separated into several major pathways serving different hippocampal regions. Recent studies show the significance of individual afferent pathways in location perception, enhancing our understanding of hippocampal function

Linking Cellular Mechanisms to Behavior: Entorhinal Persistent Spiking and Membrane Potential Oscillations May Underlie Path Integration, Grid Cell Firing, and Episodic Memory

The entorhinal cortex plays an important role in spatial memory and episodic memory functions. These functions may result from cellular mechanisms for integration of the afferent input to entorhinal cortex. This article reviews physiological data on persistent spiking and membrane potential oscillations in entorhinal cortex then presents models showing how both these cellular mechanisms could contribute to properties observed during unit recording, including grid cell firing, and how they could underlie behavioural functions including path integration. The interaction of oscillations and persistent firing could contribute to encoding and retrieval of trajectories through space and time as a mechanism relevant to episodic memory

Improving detection of mental health problems in community settings in Nepal: development and pilot testing of the community informant detection tool

Background Despite increasing efforts to expand availability of mental health services throughout the world, there continues to be limited utilization of these services by persons with mental illness and their families. Community-based detection that facilitates identification and referral of people with mental health problems has been advocated as an effective strategy to increase help-seeking and service utilization. The Community Informant Detection Tool (CIDT) was developed for the community informants to identify people with depression, psychosis, alcohol use problems, epilepsy, and child behavioral problems in community settings. The CIDT has been validated in Nepal and found to be effective in promoting treatment initiation. To facilitate replication in other settings, this paper describes the development process of CIDT and the steps to achieve comprehensibility, utility and feasibility. Methods The CIDT was developed in four steps. First, case vignettes and illustrations were created incorporating local idioms of distress for symptoms of each disorder with an expert panel of 25 Nepali mental health professionals. Second, the utility of a draft tool was assessed through focus group discussions (n = 19) and in-depth interviews (n = 6). Third, a practice run was conducted assessing applicability of the tool through IDI among purposively selected community informants (n = 8). Finally, surveys were administered to 105 community informants to assess feasibility. Results The first through third steps led to modifications in the format and presentation of the CIDT. The pilot test found CIDT to be comprehensible and feasible for detection and referral of all conditions except child behavioral problems. Female community health volunteers were recommended as the most appropriate persons to utilize the CIDT. Conclusion Community-based detection using the CIDT for persons in need of mental health care is perceived to be useful and feasible by key community stakeholders who would integrate the tool into their daily activities

The medial entorhinal cortex is necessary for temporal organization of hippocampal neuronal activity.

The superficial layers of the medial entorhinal cortex (MEC) are a major input to the hippocampus. The high proportion of spatially modulated cells, including grid cells and border cells, in these layers suggests that MEC inputs are critical for the representation of space in the hippocampus. However, selective manipulations of the MEC do not completely abolish hippocampal spatial firing. To determine whether other hippocampal firing characteristics depend more critically on MEC inputs, we recorded from hippocampal CA1 cells in rats with MEC lesions. Theta phase precession was substantially disrupted, even during periods of stable spatial firing. Our findings indicate that MEC inputs to the hippocampus are required for the temporal organization of hippocampal firing patterns and suggest that cognitive functions that depend on precise neuronal sequences in the hippocampal theta cycle are particularly dependent on the MEC

Physical Activity Levels of Older Community-dwelling Adults Are Influenced by Summer Weather Variables

Adequate daily physical activity (PA) is important for maintaining functional capacity and independence in older adults. However, most older adults in Canada do not engage in enough PA to sustain fitness and functional independence. Environmental influences, such as warmer daytime temperatures, may influence PA participation; however, few studies have examined the effect of summertime temperatures on PA levels in older adults. This investigation measured the influence of summertime weather variables on PA in 48 community-dwelling older adults who were randomly recruited from a local seniors’ community centre. Each participant wore an accelerometer for a single 7-consecutive-day period (between 30 May and 9 August 2006) during waking hours, and completed a PA logbook to remark on major daily PA events. Local weather variables were collected from a national weather service and compared with PA counts per minute. Regression analysis revealed a curvilinear relationship between log-transformed PA and mean daily temperature (r2 = 0.025; p \u3c 0.05). Linear mixed effects models that accounted for repeated measures nested within individuals were performed for monthly periods, meteorological variables, sex, age, and estimated maximal oxygen consumption, with PA as the dependent variable. Age and Air Quality Index remained significant variables within the model. Higher fitness levels had no effect on allowing individuals to perform more vigorous PA in warmer temperatures

Assembly of the Complex between Archaeal RNase P Proteins RPP30 and Pop5

RNase P is a highly conserved ribonucleoprotein enzyme that represents a model complex for understanding macromolecular RNA-protein interactions. Archaeal RNase P consists of one RNA and up to five proteins (Pop5, RPP30, RPP21, RPP29, and RPP38/L7Ae). Four of these proteins function in pairs (Pop5-RPP30 and RPP21–RPP29). We have used nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetry (ITC) to characterize the interaction between Pop5 and RPP30 from the hyperthermophilic archaeon Pyrococcus furiosus (Pfu). NMR backbone resonance assignments of free RPP30 (25 kDa) indicate that the protein is well structured in solution, with a secondary structure matching that observed in a closely related crystal structure. Chemical shift perturbations upon the addition of Pop5 (14 kDa) reveal its binding surface on RPP30. ITC experiments confirm a net 1 : 1 stoichiometry for this tight protein-protein interaction and exhibit complex isotherms, indicative of higher-order binding. Indeed, light scattering and size exclusion chromatography data reveal the complex to exist as a 78 kDa heterotetramer with two copies each of Pop5 and RPP30. These results will inform future efforts to elucidate the functional role of the Pop5-RPP30 complex in RNase P assembly and catalysis