Hippocampus

Many complex spike cells in the hippocampus of the freely moving rat have as their primary correlate the animal's location in an environment (place cells). In contrast, the hippocampal electroer cephalograph theta pattern of rhythmical waves (7–12 Hz) is better correlated with a class of movements that change the rat's location in an environment. During movement through the place field, the complex spike cells often fire in a bursting pattern with an interburst frequency in the same range as the concurrent electroencephalograph theta. The present study examined the phase of the theta wave at which the place cells fired. It was found that firing consistently began at a particular phase as the rat entered the field but then shifted in a systematic way during traversal of the field, moving progressively forward on each theta cycle. This precession of the phase ranged from 100° to 355° in different cells. The effect appeared to be due to the fact that individual cells had a higher interburst rate than the theta frequency. The phase was highly correlated with spatial location and less well correlated with temporal aspects of behavior, such as the time after place field entry. These results have implications for several aspects of hippocampal function. First, by using the phase relationship as well as the firing rate, place cells can improve the accuracy of place coding. Second, the characteristics of the phase shift constrain the models that define the construction of place fields. Third, the results restrict the temporal and spatial circumstances under which synapses in the hippocampus could be modified.

Licensed London taxi drivers show that humans have a remarkable capacity to acquire and use knowledge of a large complex city to navigate within it. Gray matter volume differences in the hippocampus relative to controls have been reported to accompany this expertise. While these gray matter differences could result from using and updating spatial representations, they might instead be influenced by factors such as self‐motion, driving experience, and stress. We examined the contribution of these factors by comparing London taxi drivers with London bus drivers, who were matched for driving experience and levels of stress, but differed in that they follow a constrained set of routes. We found that compared with bus drivers, taxi drivers had greater gray matter volume in mid‐posterior hippocampi and less volume in anterior hippocampi. Furthermore, years of navigation experience correlated with hippocampal gray matter volume only in taxi drivers, with right posterior gray matter volume increasing and anterior volume decreasing with more navigation experience. This suggests that spatial knowledge, and not stress, driving, or self‐motion, is associated with the pattern of hippocampal gray matter volume in taxi drivers. We then tested for functional differences between the groups and found that the ability to acquire new visuo‐spatial information was worse in taxi drivers than in bus drivers. We speculate that a complex spatial representation, which facilitates expert navigation and is associated with greater posterior hippocampal gray matter volume, might come at a cost to new spatial memories and gray matter volume in the anterior hippocampus. © 2006 Wiley‐Liss, Inc.

The hippocampus is one of several limbic brain structures implicated in the pathophysiology and treatment of mood disorders. Preclinical and clinical studies demonstrate that stress and depression lead to reductions of the total volume of this structure and atrophy and loss of neurons in the adult hippocampus. One of the cellular mechanisms that could account for alterations of hippocampal structure as well as function is the regulation of adult neurogenesis. Stress exerts a profound effect on neurogenesis, leading to a rapid and prolonged decrease in the rate of cell proliferation in the adult hippocampus. In contrast, chronic antidepressant treatment up‐regulates hippocampal neurogenesis, and could thereby block or reverse the atrophy and damage caused by stress. Recent studies also demonstrate that neurogenesis is required for the actions of antidepressants in behavioral models of depression. This review discusses the literature that has lead to a neurogenic hypothesis of depression and antidepressant action, as well as the molecular and cellular mechanisms that underlie the regulation of adult neurogenesis by stress and antidepressant treatment. © 2006 Wiley‐Liss, Inc.

Studies have shown that peripheral levels of corticosterone correlate with the magnitudes of two well‐described physiological models of memory, long‐term potentiation (LTP) and primed burst (PB) potentiation. In the present experiments, the authors investigated the effects of experimenter‐controlled manipulations of the levels of corticosterone on the magnitude of hippocampal PB potentiation in urethane‐anesthetized rats. Primed burst potentiation is a long‐lasting (at least 30 minutes) increase in the amplitude of the CA1 population spike and EPSP slope in response to physiologically patterned stimulation of the hippocampal commissure. The levels of serum corticosterone were controlled by implanting corticosterone pellets in adrenalectomized rats (ADX/PELLET). In the first experiment, a significant negative linear correlation between elevated (stress) levels of serum corticosterone (greater than 20 μm/dL) and the magnitude of PB potentiation in ADX/PELLET subjects (r = 0.60, P <.05) was found. In the second experiment, the shape of the corticosterone‐PB potentiation function was different at low and intermediate levels of corticosterone than it was at high levels of corticosterone: There was a positive correlation at low levels (0–10 μm/dL), a peak response at intermediate levels (11–20 μm/dL), and a negative correlation at high levels (21–93 μm/dL) of corticosterone. Thus, the overall relationship between corticosterone and PB potentiation is an inverted‐U function. These findings provide strong support for the hypothesis that corticosterone exerts a concentration‐dependent biphasic influence on the expression of hippocampal plasticity.

We review the ideas and data behind the hypothesis that hippocampal pyramidal cells encode information by their phase of firing relative to the theta rhythm of the EEG. Particular focus is given to the further hypothesis that variations in firing rate can encode information independently from that encoded by firing phase. We discuss possible explanation of the phase‐precession effect in terms of interference between two independent oscillatory influences on the pyramidal cell membrane potential, and the extent to which firing phase reflects internal dynamics or external (environmental) variables. Finally, we propose a model of the firing of the recently discovered “grid cells” in entorhinal cortex as part of a path‐integration system, in combination with place cells and head‐direction cells. © 2005 Wiley‐Liss, Inc.

It is well accepted that recognition memory reflects the contribution of two separable memory retrieval processes, namely recollection and familiarity. However, fundamental questions remain regarding the functional nature and neural substrates of these processes. In this article, we describe a simple quantitative model of recognition memory (i.e., the dual‐process signal detection model) that has been useful in integrating findings from a broad range of cognitive studies, and that is now being applied in a growing number of neuroscientific investigations of memory. The model makes several strong assumptions about the behavioral nature and neural substrates of recollection and familiarity. A review of the literature indicates that these assumptions are generally well supported, but that there are clear boundary conditions in which these assumptions break down. We argue that these findings provide important insights into the operation of the processes underlying recognition. Finally, we consider how the dual‐process approach relates to recent neuroanatomical and computational models and how it might be integrated with recent findings concerning the role of medial temporal lobe regions in other cognitive functions such as novelty detection, perception, implicit memory and short‐term memory. © 2010 Wiley‐Liss, Inc.

Understanding the empirical rules that regulate alterations of hippocampal firing fields will enhance our understanding of hippocampal function. The current study sought to extend previous research in this area by examining the effect of substituting a new stimulus for a familiar stimulus in a familiar environment. Hippocampal place cells were recorded while rats chased food pellets scattered onto the floor of a cylindrical apparatus with a white cue card affixed to the apparatus wall. Once a place cell had been recorded in the presence of the white card, the white card was replaced by a black card of the same size and shape. The place cell was then recorded in the presence of the black card. Thirty‐six cells were recorded using this procedure. All cells had stable firing fields in the presence of the white card. Both the white and black cards had stimulus control over place cell firing; generally, rotation of either card caused an equal rotation of the firing fields present. When the black card was substituted for the white card, place cells showed time‐variant changes in their spatial firing patterns. The change was such that the spatial firing patterns of the majority of place cells were similar in the presence of the white and black cards during initial black card exposures. During subsequent presentations of the black card, the spatial firing patterns associated with the 2 cards became distinct from each other. Once the differentiation of firing patterns had occurred in a given rat, all place cells subsequently recorded from that rat had different firing patterns in the presence of the white and black cards. The findings are discussed relative to sensory‐, motor‐, attentional‐, and learning‐related interpretations of hippocampal function. It is argued that the time‐variant alteration of place cell firing fields observed following exposure to a novel stimulus in this study reflects an experience‐dependent modification of place cell firing patterns.

In the hippocampus, oscillations in the theta and gamma frequency range occur together and interact in several ways, indicating that they are part of a common functional system. It is argued that these oscillations form a coding scheme that is used in the hippocampus to organize the readout from long‐term memory of the discrete sequence of upcoming places, as cued by current position. This readout of place cells has been analyzed in several ways. First, plots of the theta phase of spikes vs. position on a track show a systematic progression of phase as rats run through a place field. This is termed the phase precession. Second, two cells with nearby place fields have a systematic difference in phase, as indicated by a cross‐correlation having a peak with a temporal offset that is a significant fraction of a theta cycle. Third, several different decoding algorithms demonstrate the information content of theta phase in predicting the animal's position. It appears that small phase differences corresponding to jitter within a gamma cycle do not carry information. This evidence, together with the finding that principle cells fire preferentially at a given gamma phase, supports the concept of theta/gamma coding: a given place is encoded by the spatial pattern of neurons that fire in a given gamma cycle (the exact timing within a gamma cycle being unimportant); sequential places are encoded in sequential gamma subcycles of the theta cycle (i.e., with different discrete theta phase). It appears that this general form of coding is not restricted to readout of information from long‐term memory in the hippocampus because similar patterns of theta/gamma oscillations have been observed in multiple brain regions, including regions involved in working memory and sensory integration. It is suggested that dual oscillations serve a general function: the encoding of multiple units of information (items) in a way that preserves their serial order. The relationship of such coding to that proposed by Singer and von der Malsburg is discussed; in their scheme, theta is not considered. It is argued that what theta provides is the absolute phase reference needed for encoding order. Theta/gamma coding therefore bears some relationship to the concept of “word” in digital computers, with word length corresponding to the number of gamma cycles within a theta cycle, and discrete phase corresponding to the ordered “place” within a word. © 2005 Wiley‐Liss, Inc.

The sources of ipsilateral projections from the hippocampal formation, the presubiculum, area 29a‐c, and parasubiculum to medial, orbital, and lateral prefrontal cortices were studied with retrograde tracers in 27 rhesus monkeys. Labeled neurons within the hippocampal formation (CA1, CA1′, prosubiculum, and subiculum) were found rostrally, although some were noted throughout the entire rostrocaudal extent of the hippocampal formation. Most labeled neurons in the hippocampal formation projected to medial prefrontal cortices, followed by orbital areas. In addition, there were differences in the topography of afferent neurons projecting to medial when compared with orbital cortices. Labeled neurons innervating medial cortices were found mainly in the CA1′ and CA1 fields rostrally, but originated in the subicular fields caudally. In contrast, labeled neurons which innervated orbital cortices were considerably more focal, emanating from the same relative position within a field throughout the rostrocaudal extent of the hippocampal formation.

In marked contrast to the pattern of projection to medial and orbital prefrontal cortices, lateral prefrontal areas received projections from only a few labeled neurons found mostly in the subicular fields. Lateral prefrontal cortices, lateral prefrontal cortices received the most robust projections from the presubiculum and the supracallosal area 29a‐c. Orbital, and to a lesser extent medial, prefrontal areas received projections from a smaller but significant number of neurons from the presubiculum and area 29a‐c. Only a few labeled neurons were found in the parasubiculum, and most projected to medial prefrontal areas.

The results suggest that functionally distinct prefrontal cortices receive projections from different components of the hippocampal region. Medial and orbital prefrontal cortices may have a role in long‐term mnemonic process similar to those associated with the hippocampal formation with which they are linked. Moreover, the preponderance of projection neurons from the hippocampal formation innervating medial when compared with orbital prefrontal areas followed the opposite trend from what we had observed previously for the amygdala (Barbas and De Olmos [1990]) (J Comp Neurol 301:1–23). Thus, the hippocampal formation, associated with mnemonic processes, targets predominantly medial prefrontal cortices, whereas the amygdala, associated with emotional aspects of memory, issues robust projections to orbital limbic cortices. Lateral prefrontal cortices receive robust projections from the presubiculum and area 29a‐c and sparse projections from the hippocampal formation. These findings are consistent with the idea that the role of lateral prefrontal cortices in memory is distinct from that of either medial or orbital cortices. The results suggest that signals from functionally distinct limbic structures to some extent follow parallel pathways to functionally distinct prefrontal cortices. © 1995 Wiley‐Liss, Inc.

Numerous studies have reported a smaller hippocampal volume in Alzheimer's disease (AD) patients than in aging controls. However, in mild cognitive impairment (MCI), the results are inconsistent. Moreover, the left‐right asymmetry of the hippocampus receives less research attention. In this article, meta‐analyses are designed to determine the extent of hippocampal atrophy in MCI and AD, and to evaluate the asymmetry pattern of the hippocampal volume in control, MCI, and AD groups. From 14 studies including 365 MCI patients and 382 controls, significant atrophy is found in both the left [Effect size (ES), 0.92; 95% confidence interval (CI), 0.72–1.11] and right (ES, 0.78; 95% CI, 0.57–0.98) hippocampus, which is lower than that in AD (ES, 1.60, 95% CI, 1.37–1.84, in left; ES, 1.52, 95% CI, 1.31–1.72, in right). Comparing with aging controls, the average volume reduction weighted by sample size is 12.9% and 11.1% in left and right hippocampus in MCI, and 24.2% and 23.1% in left and right hippocampus in AD, respectively. The findings show a bilateral hippocampal volume loss in MCI and the extent of atrophy is less than that in AD. By comparing the left and right hippocampal volume, a consistent left‐less‐than‐right asymmetry pattern is found, but with different extents in control (ES, 0.39), MCI (ES, 0.56), and AD (ES, 0.30) group. © 2009 Wiley‐Liss, Inc.