Hippocampus最新文献

Early protein malnutrition has been shown to affect the brain reward circuitry, leading to enduring molecular, neurochemical, and behavioral alterations. This study explored how maternal protein restriction contributes to anhedonia, a key depression symptom, focusing on the hippocampal BDNF–TrkB signaling and structural plasticity changes in the CA1 subregion of the dorsal hippocampus (DH). To achieve our goal, adult rats submitted to a protein restriction schedule from the 14th day of gestation up to 30 days of age (PR-rats) were subjected to the sucrose preference test (SPT) and compared with animals fed a normoprotein diet. Immediately after SPT, we assessed the levels of BDNF and its receptor TrkB and structural plasticity changes. Interestingly, PR-rats showed a significant decrease in sucrose preference. Furthermore, perinatal protein-restriction-induced anhedonia correlated with decreased BDNF and p-TrkB levels in the DH, alongside reduced dendritic spine density in CA1 pyramidal neurons, particularly mature spines (i.e., stubby and mushroom spines). These findings suggest that decreased hippocampal BDNF–TrkB signaling accompanied by structural remodeling in the CA1 pyramidal neurons may contribute to the reduced ability of undernourished animals to respond to rewarding stimuli, increasing their vulnerability to anhedonia later in life.

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.