The hippocampus is critical for memory tasks which require an active maintenance of memory for a short period of time; however, the underlying neural mechanisms remain unknown. Most theoretical and computational models, which date back to the classic proposals by Donald Hebb in , have been self-constrained by anatomy, as most models rely on the recurrent connectivity in region CA3 to support "reverberating activity" capable of memory maintenance. However, several physiological and behavioral studies have specifically implicated region CA1 in tasks which require an active maintenance of memory. Here, we demonstrate that despite limited recurrent connectivity, CA1 contains a robust cellular mechanism for active memory maintenance in the form of self-sustained persistent firing. Using in vitro whole-cell recordings, we demonstrate that brief stimulation (0.2-2 s) reliably elicits long-lasting (> 30 s) persistent firing that is supported by the calcium-activated non-selective cationic current. In contrast to more traditional ideas, these data suggest that the hippocampal region CA1 is capable of active maintenance of memory.

Suppression of cholinergic receptors and inactivation of the septum impair short-term memory, and disrupt place cell and grid cell activity in the medial temporal lobe (MTL). Location-dependent hippocampal place cell firing during active waking, when the acetylcholine level is high, switches to time-compressed replay activity during quiet waking and slow-wave-sleep (SWS), when the acetylcholine level is low. However, it remains largely unknown how acetylcholine supports short-term memory, spatial navigation, and the functional switch to replay mode in the MTL. In this paper, we focus on the role of the calcium-activated non-specific cationic (CAN) current which is activated by acetylcholine. The CAN current is known to underlie persistent firing, which could serve as a memory trace in many neurons in the MTL. Here, we review the CAN current and discuss possible roles of the CAN current in short-term memory and spatial navigation. We further propose a novel theoretical model where the CAN current switches the hippocampal place cell activity between real-time and time-compressed sequential activity during encoding and consolidation, respectively.

During working memory tasks, the hippocampus exhibits synchronous theta-band activity, which is thought to be correlated with the short-term memory maintenance of salient stimuli. Recent studies indicate that the hippocampus contains the necessary circuitry allowing it to generate and sustain theta oscillations without the need of extrinsic drive. However, the cellular and network mechanisms supporting synchronous rhythmic activity are far from being fully understood. Based on electrophysiological recordings from hippocampal pyramidal CA1 cells, we present a possible mechanism for the maintenance of such rhythmic theta-band activity in the isolated hippocampus. Our model network, based on the Hodgkin-Huxley formalism, comprising pyramidal neurons equipped with calcium-activated nonspecific cationic (CAN) ion channels, is able to generate and sustain synchronized theta oscillations (4-12 Hz), following a transient stimulation. The synchronous network activity is maintained by an intrinsic CAN current (I ), in the absence of constant external input. When connecting the pyramidal-CAN network to fast-spiking inhibitory interneurons, the dynamics of the model reveal that feedback inhibition improves the robustness of fast theta oscillations, by tightening the synchronization of the pyramidal CAN neurons. The frequency and power of the theta oscillations are both modulated by the intensity of the I , which allows for a wide range of oscillation rates within the theta band. This biologically plausible mechanism for the maintenance of synchronous theta oscillations in the hippocampus aims at extending the traditional models of septum-driven hippocampal rhythmic activity. © 2017 Wiley Periodicals, Inc.

Metals are found ubiquitously throughout an organism, with their biological role dictated by both their chemical reactivity and abundance within a specific anatomical region. Within the brain, metals have a highly compartmentalized distribution, depending on the primary function they play within the central nervous system. Imaging the spatial distribution of metals has provided unique insight into the biochemical architecture of the brain, allowing direct correlation between neuroanatomical regions and their known function with regard to metal-dependent processes. In addition, several age-related neurological disorders feature disrupted metal homeostasis, which is often confined to small regions of the brain that are otherwise difficult to analyze. Here, we describe a comprehensive method for quantitatively imaging metals in the mouse brain, using laser ablation - inductively coupled plasma - mass spectrometry (LA-ICP-MS) and specially designed image processing software. Focusing on iron, copper and zinc, which are three of the most abundant and disease-relevant metals within the brain, we describe the essential steps in sample preparation, analysis, quantitative measurements and image processing to produce maps of metal distribution within the low micrometer resolution range. This technique, applicable to any cut tissue section, is capable of demonstrating the highly variable distribution of metals within an organ or system, and can be used to identify changes in metal homeostasis and absolute levels within fine anatomical structures.