Hippocampus最新文献

Numerous scientific advances and discoveries have arisen from research on the hippocampal formation. This special issue provides first-person historical descriptions of these advances and discoveries in hippocampal research, written by those directly involved in the research. This is the first section of a special issue that will also include future articles on this topic. Here, we discuss some of the factors that motivated this special issue, and the major themes of hippocampal research that are addressed.

In 1979, I joined Jim Ranck's group in Brooklyn and began recording hippocampal neurons. The first project was to record single neurons across three behaviors in different chambers: pellet retrieval on a radial-arm maze, bar-pressing for food reward in an operant chamber, and maternal pup-retrieval in a large home box. We found spatial firing in all three chambers, with a single-neuron's firing pattern unpredictable from one chamber to the next. We interpreted the spatial firing patterns as representing “context.” Later, in the 1980s, I began collaborating with Bob Muller (and Jim Ranck). In the first of a pair of 1987 papers, we used computerized data acquisition, recorded in simple, reduced environments to demonstrate robust, stable place cell firing and the characteristic features of firing fields. In the second paper we showed that when a rat is transferred from one environment to another, the set of place cells “remaps.” “Remapping” was defined later, in a pair of 1990 papers. “Context” was introduced in the early three-behavior experiment but was not discussed in the 1987 papers. What is the true relationship between the biological observation of “remapping” and the psychological concept of “context”? This difficult question is addressed here and in more detail in our recent paper.

In keeping with the historical focus of this special issue of Hippocampus, this paper reviews the history of my development of the SPEAR model. The SPEAR model proposes that separate phases of encoding and retrieval (SPEAR) allow effective storage of multiple overlapping associative memories in the hippocampal formation and other cortical structures. The separate phases for encoding and retrieval are proposed to occur within different phases of theta rhythm with a cycle time on the order of 125 ms. The same framework applies to the slower transition between encoding and consolidation dynamics regulated by acetylcholine. The review includes description of the experimental data on acetylcholine and theta rhythm that motivated this model, the realization that existing associative memory models require these different dynamics, and the subsequent experimental data supporting these dynamics. The review also includes discussion of my work on the encoding of episodic memories as spatiotemporal trajectories, and some personal description of the episodic memories from my own spatiotemporal trajectory as I worked on this model.

For many years, the hilus of the dentate gyrus (DG) was a mystery because anatomical data suggested a bewildering array of cells without clear organization. Moreover, some of the anatomical information led to more questions than answers. For example, it had been identified that one of the major cell types in the hilus, the mossy cell, innervates granule cells (GCs). However, mossy cells also targeted local GABAergic neurons. Furthermore, it was not yet clear if mossy cells were glutamatergic or GABAergic. This led to many debates about the role of mossy cells. However, it was clear that hilar neurons, including mossy cells, were likely to have very important functions because they provided strong input to GCs. Hilar neurons also attracted attention in epilepsy because pathological studies showed that hilar neurons were often lost, but GCs remained. Vulnerability of hilar neurons also occurred after traumatic brain injury and ischemia. These observations fueled an interest to understand hilar neurons and protect them, an interest that continues to this day. This article provides a historical and personal perspective into the ways that I sought to contribute to resolving some of the debates and moving the field forward. Despite several technical challenges the outcomes of the studies have been worth the effort with some surprising findings along the way. Given the growing interest in the hilus, and the advent of multiple techniques to selectively manipulate hilar neurons, there is a great opportunity for future research.

For most of my career, I focused on understanding how and where spatial context, the place where things happen, is represented in the brain. My interest in this began in the early 1990's, during my postdoctoral training with David Amaral, when we defined the rodent homolog of the primate parahippocampal cortex, a region implicated in processing spatial and contextual information. We parceled out the caudal portion of the rat perirhinal cortex (PER) and called it the postrhinal cortex (POR). In my own lab at Brown University, I continued to study the anatomy of the PER, POR, and entorhinal cortices. I also began to characterize and differentiate the functions of these regions, particularly the newly defined POR and the redefined PER. Our electrophysiological and behavioral evidence supports a view of POR function that aligns with our anatomical evidence. Briefly, the POR integrates object and feature information from the PER with spatial information from the retrosplenial, posterior parietal, and secondary visual cortices and the pulvinar and uses this information to represent specific environmental contexts, including the spatial arrangement of objects and features within each context. In addition to maintaining a representation of the current context, the POR plays an attentional role by continually monitoring the context for changes and updating the context representation when changes occur. This context representation is accessible to other regions for cognitive processes, including binding life events with context to form episodic memories, guiding context-relevant behavior, and recognizing objects within scenes and contexts.

As requested by the editors of this special issue of Hippocampus on Scientific Histories of Hippocampal Research, this review provides a detailed personal perspective and historical background on the research involved in a number of findings. The review includes description of the development of the water maze and its use in providing evidence to support the role of the hippocampus in spatial memory function. The review also describes how the water maze was then used in further work to support the proposal that NMDA-dependent synaptic modification in the hippocampus mediates the encoding of new spatial memories. This personal history gives a perspective on the convergence of different streams of physiological, biochemical, theoretical and behavioral research that resulted in these findings on hippocampal function.

Accumulating evidence indicates that inherited astrocyte dysfunction can be a primary trigger for epilepsy development; however, the available data are rather limited. In addition, astrocytes are considered as a perspective target for the design of novel and improvement of the existing antiepileptic therapy. Piracetam and related nootropic drugs are widely used in the therapy of various epileptic disorders, but detailed mechanisms of racetams action and, in particular, their effects on glial functions are poorly understood. In this study, we explored the functional state of astrocytes in the dentate gyrus (DG) of Krushinsky–Molodkina (KM) rats genetically prone to audiogenic seizures and compared the action of piracetam on the DG astrocytes in KM and normal Wistar rats. Wistar and naïve KM rats which received injections of saline (control) or piracetam (100 mg/kg) for 21 days were recruited in our studies. Comparative analysis of control Wistar and KM rats revealed genetically determined abnormalities in DG astrocytes of KM rats including an increased expression of NFIA but a decreased GFAP, ALDH1L1, EAATs, and glutamine synthetase (GS). Piracetam treatment normalized the expression of all studied markers, except NFIA, in KM rats, while in Wistar rats, it potentiated only GS and NFIA. The results suggested that the nootropic and antiepileptic effects of piracetam may be, at least partially, mediated by the modulation of astroglia functions. In addition, analysis of NFIA and GS colocalization revealed the novel pattern of astrocyte heterogeneity in the DG which was significantly altered in epileptic rats but corrected by piracetam.

This article is my recollection of events surrounding the discovery of head direction (HD) cells by Jim Ranck in 1984 and the first journal publications 6 years later. Ranck first described the fundamental properties of HD cells qualitatively in a Society for Neuroscience abstract (1984) and in the proceedings to a conference. Ranck, however, was convinced by Bob Muller, a faculty colleague in the lab, to delay writing up Jim's discovery until they developed a two-spot video tracking system, which would enable proper quantitative analyses. The development of this system was complex and was still undergoing development when I arrived in the Brooklyn lab in 1986. By this time, Jim had begun to refocus his efforts on thinking about the relationship between space and manifolds and was no longer engaged in active research. It thus befell me (unintentionally) to complete the recordings of these fascinating cells. This endeavor involved recording additional HD cells with the new video tracking system, monitoring the cells' responses following a series of environmental manipulations, and performing quantitative analyses on the data. Throughout 1987, I recorded most of the cells that would form the basis for our 1990 papers published in the Journal of Neuroscience. Along the way, there were many events and emotions: luck, excitement, humor, frustration, tutorials, unintended outcomes, and long-lasting friendships. I was guided and supported during this time by both Bob Muller and John Kubie, but remain forever grateful to Jim for this wonderful opportunity.