Mechanisms underlying grid cell firing in the medial entorhinal cortex (MEC)

Mechanisms underlying grid cell firing in the medial entorhinal cortex (MEC) still remain unknown. clamp recordings in rats. Anatomical distributions of these properties were compared along both the dorso-ventral and medio-lateral axes both with and without the cholinergic receptor agonist carbachol. We found that spike frequency adaptation is significantly stronger in ventral than in dorsal neurons both with and without carbachol. Spike frequency adaptation was significantly correlated with the duration from the mAHP which also demonstrated a gradient along the dorso-ventral axis. In carbachol we discovered that about 50% of MEC coating II neurons display continual firing which lasted a lot more than 30 mere seconds. Continual firing of MEC layer II neurons may donate to grid cell firing by giving the excitatory travel. Dorso-ventral variations in spike rate of recurrence adaptation we record here are opposing from earlier predictions with a computational model. We talk about an alternative system concerning how dorso-ventral variations in spike rate of recurrence adaptation could donate to different scales of grid spacing. Intro Grid cells within the medial entorhinal cortex (MEC) layer II are suggested to play an important role in spatial navigation [1]. Grid cell firing has been proposed to be generated within the MEC local circuit [2]-[5]. Cellular properties of MEC neurons such as subthreshold membrane potential oscillations (SMPOs) [2] [3] [6] resonance [6]-[8] input resistance [9] firing frequency adaptation [10] and persistent firing [11] may play an important role in grid cell firing. The SMPO frequency the resonance frequency and the input resistance have been reported to vary systematically along the dorso-ventral (DV) axis and are suggested to underlie the gradient of spacing of grid cell firing fields at different positions along the DV axis [6] [9] [12] [13]. A recent study on HCN1 channel KO mice with reduced subthreshold membrane potential oscillations (SMPOs) and resonance has shown a wider spacing of LX 1606 grid cells further suggesting that cellular properties play crucial roles in grid cell firing [14]. However what determines the gradient of grid cell spacing remains unknown since the grid spacing difference was maintained in this study [14]. Moreover the anatomical gradient of several from the cellular properties of MEC layer II cells have not been studied along the medio-lateral (ML) axis [7]. Recent in vivo LX 1606 intracellular recordings have shown that grid cells have properties predicted by both continuous attractor models and oscillatory interference models [15] suggesting that a hybrid of both models may explain experimental observations better [16]. Of note is the sustained depolarization seen as the animal crossed the grid field [15] which was predicted by continuous attractor models. Such depolarization in continuous attractor models are usually supported by recurrent excitatory connections. However excitatory recurrent connections are virtually nonexistent in the MEC layer II [17] [18] [19] and it remains unknown where such excitatory drive comes from. Recent work has shown that inactivation of the medial septum which provides cholinergic projections to the MEC disrupts grid cell activity [20] [21]. Lesions of the basal forebrain cholinergic system disrupt idiothetic navigation in mice [22]. Although cholinergic modulation of SMPO along the DV axis has been reported [23] the differential effect of cholinergic activation on other cellular properties along the DV axis remains unknown. Cholinergic modulation may also provide depolarization drive through persistent firing [16]. However persistent firing in MEC layer II neurons has not been studied thoroughly. In this paper we investigated cellular properties of MEC layer II neurons at different two dimensional (DV and ML) anatomical positions across the extent of the MEC. Properties were tested with and without the cholinergic agonist carbachol using whole-cell patch recording in vitro. Cellular properties studied included spike frequency adaptation SMPOs input resistance sag ratio and persistent firing. We Rabbit Polyclonal to OR7A10. find that spike frequency adaptation is stronger in ventral compared to dorsal MEC and the amplitude and the duration of the medium after hyperpolarization (mAHP; [24] LX 1606 [25]) both vary systematically along the DV axis along with input resistance and SMPO LX 1606 frequency. None of these properties showed a clear difference along the ML axis. More than half (54%) of the layer II neurons showed long-lasting (>30 s) persistent firing in.