Age‐related alterations in functional connectivity along the longitudinal axis of the hippocampus and its subfields

Hippocampal circuit alterations that differentially affect hippocampal subfields are associated with age‐related memory decline. Additionally, functional organization along the longitudinal axis of the hippocampus has revealed distinctions between anterior and posterior (A‐P) connectivity. Here, we examined the functional connectivity (FC) differences between young and older adults at high‐resolution within the medial temporal lobe network (entorhinal, perirhinal, and parahippocampal cortices), allowing us to explore how hippocampal subfield connectivity across the longitudinal axis of the hippocampus changes with age. Overall, we found reliably greater connectivity for younger adults than older adults between the hippocampus and parahippocampal cortex (PHC) and perirhinal cortex (PRC). This drop in functional connectivity was more pronounced in the anterior regions of the hippocampus than the posterior ones, consistent for each of the hippocampal subfields. Further, intra‐hippocampal connectivity also reflected an age‐related decrease in functional connectivity within the anterior hippocampus in older adults that was offset by an increase in posterior hippocampal functional connectivity. Interestingly, the anterior–posterior dysfunction in older adults between hippocampus and PHC was predictive of lure discrimination performance on the Mnemonic similarity task (MST), suggesting a role in memory performance. While age‐related dysfunction within the hippocampal subfields has been well‐documented, these results suggest that the age‐related dysfunction in hippocampal connectivity across the longitudinal axis may also contribute significantly to memory decline in older adults.     

Differential modulation of CA1 impulse flow by endogenous serotonin along the hippocampal longitudinal axis

The hippocampus is functionally differentiated along its longitudinal axis, with the dorsal and ventral segments preferentially involved in cognitive and emotional processing, respectively. Serotonergic modulation of hippocampal function has been extensively studied, but its relation to the dorsoventral axis has remained largely unknown. To examine the modulation of hippocampal output along the dorsoventral axis by endogenous serotonin (5‐HT) we compared the effect of the 5‐HT/noradrenaline (NA)‐releaser, 3,4‐methylenedioxymethamphetamine (MDMA), in transversal slices encompassing the entire rat hippocampus. Co‐release of 5‐HT and NA by MDMA resulted in a gradient of effects on evoked population spikes in the CA1 area along the dorsoventral axis of the hippocampus. Selective 5‐HT release decreased population spike amplitude in slices from dorsal hippocampus, whereas an increase was produced in the ventral hippocampus, indicating differential modulation of CA1 impulse flow along the dorsoventral axis by endogenous 5‐HT. Selective NA release increased population spike amplitude with no gradient indicating facilitatory effect of endogenous NA along the entire dorsoventral axis. Blockade of 5‐HT_1A receptors prevented the inhibitory component of MDMA action and the emergence of the gradient, indicating that activation of 5‐HT_1A receptors is required for differential modulation of CA1 impulse flow by endogenous 5‐HT. These findings suggest that a dorsoventral shift in CA1 output level may represent an integral component of 5‐HT action on hippocampal information processing. Given the preferential role of ventral hippocampus in emotional and anxiety‐related behavior, it can be proposed that serotonin tone encodes the emotional salience of the signal processed by hippocampus.     

Origin of microglia in the quail retina: Central-to-peripheral and vitreal-to-scleral migration of microglial precursors during development

Collateral sprouting of dentate granule cell axons, the mossy fibers, occurs in response to denervation, kindling, or excitotoxic damage to the hippocampus. Organotypic slice culture of rodent hippocampal tissue is a model system for the controlled study of collateral sprouting in vitro. Organotypic roller-tube cultures were prepared from hippocampal slices derived from postnatal day 7 mice. The Timm heavy metal stain and densitometry were used to assay the degree of mossy fiber collateral sprouting in the molecular layer of the hippocampal dentate gyrus. Factors influencing mossy fiber collateral sprouting were time in culture, positional origin of the slice culture along the septotemporal axis of the hippocampus, and presence of attached subicular-entorhinal cortical tissues. Collateral sprouting in the molecular layer was first detected after 6 days in culture and increased steadily thereafter. By 2 weeks considerable sprouting was apparent, and at 3 weeks intense sprouting was observed within the molecular layer. An intrinsic septal-to-temporal gradient of collateral sprouting was apparent at 14 days in culture. To determine whether differential damage to the mossy fibers was the basis for the differences in collateral sprouting along the septotemporal axis, we made complete transections of the mossy fiber projection as it exited the dentate hilus at various levels along the septotemporal axis; no differences were found on subsequent collateral sprouting in the dentate molecular layer. Timm-stained hippocampal cultures with an attached entorhinal cortex, a major source of afferent innervation to the dentate granule cells, displayed significantly less collateral sprouting at 10 days in culture compared to that in cultures from adjacent sections without attached subicular-entorhinal tissues present. Thus, time in culture, position along the septotemporal axis, and presence of afferent cortical tissues influence aberrant neurite collateral sprouting in organotypic slice cultures of neonatal mouse hippocampus. © Wiley-Liss, Inc.     

Can the hippocampus tell time? The temporo-septal engram shift model.

An essential feature of episodic memory, the type of memory dependent on hippocampus, is that individual memories belong to particular moments in time. Recent PET studies suggest that memory encoding and recall occur at different locations in human hippocampus. Coupled with other attributes of hippocampus, this suggested to us that the septo-temporal hippocampal axis may play an important role in time perception. We propose a temporo-septal engram shift model of hippocampal memory. The model posits that memories gradually move along the hippocampus from a temporal encoding site to ever more septal sites from which they are recalled. We propose that the sense of time is encoded by the location of the engram along the temporo-septal axis.     

NADPH-Diaphorase in the central nervous system of the larval lamprey (Lampetra planeri)

The anatomy of the hippocampus, including the organization of its intrinsic neural circuits and afferents, is organized along a rostrocaudal axis. Dopamine D2 receptors are expressed in specific regions of the hippocampal complex (hippocampal subfields, entorhinal cortex, perirhinal cortex) and show differential expression along this axis. The dentate gyrus and CA3/CA4 subfields show higher numbers of D2 receptors in the rostral than in the caudal levels. In contrast, the subiculum shows the reverse gradient. We report here that Alzheimer's disease (AD) is associated with reduced expression of the dopamine D2 receptor, but the effects differ with respect to the rostrocaudal axis and area within the hippocampal complex. The number of D2 receptors is significantly reduced in the molecular layer of the dentate gyrus, CA3 subfield, and subiculum. For the dentate gyrus and subiculum, there were greater losses at more rostral levels. The CA3/CA4 subfields showed the greatest losses caudally. The entorhinal cortex, which shows only modest expression of D2 receptors in controls, does not exhibit reduced numbers in AD. The external laminae of the rostral perirhinal cortex showed more significant losses than more caudally in this cortical field. The regions showing loss of D2 receptors do not typically contain neuritic plaques, neurofibrillary tangles, or significant neuron loss. Thus other mechanisms must account for the unique gradient of D2 receptor loss in the hippocampus. The regions of reduced expression of dopamine D2 receptors do correlate well with the terminal zone of the dentate association pathway, the afferents from the anlygdala and perirhinal cortex, and the sources of those afferents within the amygdala and perirhinal cortex. The specific patterns of reduced D2 receptor expression in AD are likely to contribute significantly to the disrupted information flow into and out of the hippocampus and, thus, of functions subserved by this system. © 1994 Wiley-Liss, Inc.     

Differential propagation of ripples along the proximodistal and septotemporal axes of dorsal CA1 of rats

The functional connectivity of the hippocampus with its primary cortical input, the entorhinal cortex, is organized topographically. In area CA1 of the hippocampus, this leads to different functional gradients along the proximodistal and septotemporal axes of spatial/sensory responsivity and spatial resolution respectively. CA1 ripples, a network phenomenon, allow us to test whether the hippocampal neural network shows corresponding gradients in functional connectivity along the two axes. We studied the occurrence and propagation of ripples across the entire proximodistal axis along with a comparable spatial range of the septotemporal axis of dorsal CA1. We observed that ripples could occur at any location, and their amplitudes were independent of the tetrode location along the proximodistal and septotemporal axes. When a ripple was detected on a particular tetrode (“reference tetrode”), however, the probability of cooccurrence of ripples and ripple amplitude observed on the other tetrodes decreased as a function of distance from the reference tetrode. This reduction was greater along the proximodistal axis than the septotemporal axis. Furthermore, we found that ripples propagate primarily along the proximodistal axis. Thus, over a spatial scale of ～1.5 mm, the network is anisotropic along the two axes, complementing the topographically organized cortico‐hippocampal connections.     

Chrna2‐OLM interneurons display different membrane properties and h‐current magnitude depending on dorsoventral location

The hippocampus is an extended structure displaying heterogeneous anatomical cell layers along its dorsoventral axis. It is known that dorsal and ventral regions show different integrity when it comes to functionality, innervation, gene expression, and pyramidal cell properties. Still, whether hippocampal interneurons exhibit different properties along the dorsoventral axis is not known. Here, we report electrophysiological properties of dorsal and ventral oriens lacunosum moleculare (OLM) cells from coronal sections of the Chrna2‐cre mouse line. We found dorsal OLM cells to exhibit a significantly more depolarized resting membrane potential compared to ventral OLM cells, while action potential properties were similar between the two groups. We found ventral OLM cells to show a higher initial firing frequency in response to depolarizing current injections but also to exhibit a higher spike‐frequency adaptation than dorsal OLM cells. Additionally, dorsal OLM cells displayed large membrane sags in response to negative current injections correlating with our results showing that dorsal OLM cells have more hyperpolarization‐activated current (I_h) compared to ventral OLM cells. Immunohistochemical examination indicates the h‐current to correspond to hyperpolarization‐activated cyclic nucleotide‐gated subunit 2 (HCN2) channels. Computational studies suggest that I_h in OLM cells is essential for theta oscillations in hippocampal circuits, and here we found dorsal OLM cells to present a higher membrane resonance frequency than ventral OLM cells. Thus, our results highlight regional differences in membrane properties between dorsal and ventral OLM cells allowing this interneuron to differently participate in the generation of hippocampal theta rhythms depending on spatial location along the dorsoventral axis of the hippocampus.     

Ictal fear in temporal lobe epilepsy: surgical outcome and focal hippocampal changes revealed by proton magnetic resonance spectroscopy imaging

BACKGROUND: Ictal fear (IF) is most frequently associated with epileptic discharges from mesial temporal areas. OBJECTIVES: To determine whether patients with IF were more likely to become seizure free after anteromesial temporal lobe resection compared with those without IF and whether they show more anteriorly pronounced metabolic changes assessed by means of multivoxel magnetic resonance spectroscopy (MRS) along the hippocampal axis. METHODS: Surgical outcome was assessed in 33 consecutive patients with temporal lobe epilepsy after a mean follow-up of 25 months (range, 12-38 months). Proton multivoxel MRS of the hippocampal formation was applied to detect regional differences along the axis of the hippocampus in patients with and without IF. Magnetic resonance tomography showed typical features of hippocampal sclerosis in all patients. RESULTS: Twelve (36%) of the 33 patients reported fear at the beginning of their habitual seizures. Eleven of these patients were seizure free postoperatively. In contrast, only 11 of 21 patients without IF had a favorable outcome. Results of MRS revealed significantly higher pathologic N-acetylaspartate-choline ratios in the anterior portion of the hippocampal formation in patients with than in those without IF, indicating focal metabolic and/or morphologic changes in the head of the hippocampus. CONCLUSIONS: These results indicate the importance of diagnosing auras with IF to provide a more detailed prognosis of the surgical outcome. In addition, our data emphasize that multivoxel MRS is a valuable tool in the presurgical evaluation, as it may reveal different topographical patterns of hippocampal sclerosis.     

Theta band power increases in the posterior hippocampus predict successful episodic memory encoding in humans

Functional differences in the anterior and posterior hippocampus during episodic memory processing have not been examined in human electrophysiological data. This is in spite of strong evidence for such differences in rodent data, including greater place cell specificity in the dorsal hippocampus, greater sensitivity to the aversive or motivational content of memories in ventral regions, connectivity analyses identifying preferential ventral hippocampal connections with the amygdala, and gene expression analyses identifying a dorsal–ventral gradient. We asked if memory‐related oscillatory patterns observed in human hippocampal recordings, including the gamma band and slow‐theta (2.5–5 Hz) subsequent memory effects, would exhibit differences along the longitudinal axis and between hemispheres. We took advantage of a new dataset of stereo electroencephalography patients with simultaneous, robotically targeted anterior, and posterior hippocampal electrodes to directly compare oscillatory subsequent memory effects during item encoding. This same data set allowed us to examine left–right connectivity and hemispheric differences in hippocampal oscillatory patterns. Our data suggest that a power increase during successful item encoding in the 2.5–5 Hz slow‐theta frequency range preferentially occurs in the posterior hippocampus during the first 1,000 ms after item presentation, while a gamma band power increase is stronger in the dominant hemisphere. This dominant–nondominant pattern in the gamma range appears to reverse during item retrieval, however. Intrahippocampal phase coherence was found to be stronger during successful item encoding. Our phase coherence data are also consistent with existing reports of a traveling wave for theta oscillations propagating along the septotemporal (longitudinal) axis of the human hippocampus. We examine how our findings fit with theories of functional specialization along the hippocampal axis.     

Topographic analysis of cell proliferation in the hippocampus of the adult mouse

The dentate gyrus of the hippocampus generates new neurons throughout life. The distribution of neural progenitor cells in the hippocampus along the anteroposterior axis is, however, not known. To determine whether mitotic activity differs along the anteroposterior axis, we examined mitotic activity in serial hippocampal sections of two experimental groups: normal bred (control) and exercised groups. In both groups, the number of 5-bromo-2'-deoxyuridine-positive cells was markedly decreased in the caudal dentate gyrus; exercised groups also had mitotic activity of about 1.5 times that of control groups. Mitotic activity tended to increase in the suprapyramidal blade of the middle dentate gyrus of exercised groups. These results indicate that the adult hippocampus has regional differences in mitotic activity.     

Hippocampal involvement in detection of deviant auditory and visual stimuli

Recent models of hippocampal function have emphasized its role in processing sequences of events. In this study, we used an oddball task to investigate hippocampal responses to the detection of deviant "target" stimuli that were embedded in a sequence of repetitive "standard" stimuli. Evidence from intracranial event-related potential studies has suggested a critical role for the hippocampus in oddball tasks. However, functional neuroimaging experiments have failed to detect activation in the hippocampus in response to deviant stimuli. Our study aimed to resolve this discrepancy by using a novel functional magnetic resonance imaging (fMRI) technique that drastically improves signal detection in the hippocampus. Significant hippocampal activation was observed during both auditory and visual oddball tasks. Although there was no difference in the overall level of hippocampal activation in the two modalities, significant modality differences in the profile of activation along the long axis of the hippocampus were observed. In both left and right hippocampi, an anterior-to-posterior gradient in the activation (anterior to posterior) was observed during the auditory oddball task, whereas a posterior-to-anterior gradient (posterior to anterior) was observed during the visual oddball task. These results indicate that the hippocampus is involved in the detection of deviant stimuli regardless of stimulus modality, and that there are prominent modality differences along the long axis of the hippocampus. The implications of our findings for understanding hippocampal involvement in processing sequences of events are discussed.     

Effects of endogenous and exogenous D1/D5 dopamine receptor activation on LTP in ventral and dorsal CA1 hippocampal synapses

Hippocampus is importantly involved in dopamine‐dependent behaviors and dopamine is a significant modulator of synaptic plasticity in the hippocampus. Moreover, the dopaminergic innervation appears to be disproportionally segregated along the hippocampal longitudinal (dorsoventral) axis with unknown consequences for synaptic plasticity. In this study we examined the actions of endogenously released dopamine and the effects of exogenous D1/D5 dopamine receptor agonists on theta‐burst stimulation‐induced long‐term potentiation (LTP) of field excitatory synaptic potential (fEPSP) at Schaffer collateral‐CA1 synapses in slices from dorsal (DH) and ventral hippocampus (VH). Furthermore, we quantified D1 receptor mRNA and protein expression levels in DH and VH. We found that blockade of D1/D5 receptors by SCH 23390 (20 μM) significantly reduced the magnitude of LTP in both DH and VH similarly suggesting that dopamine endogenously released during TBS, presumably mimicking low activity of DA neurons, exerts a homogeneous modulation of LTP along the hippocampal long axis. Moderate to high concentrations of the selective partial D1/D5 receptor agonist SKF 38393 (50‐150 μM) did not significantly change LTP in either hippocampal segment. However, the full D1 receptor selective agonist SKF 82958 (10 μM) significantly enhanced LTP in VH but not DH. Furthermore, the expression of D1 receptor mRNA and protein was considerably higher in VH compared with DH. These results suggest that the dynamic range of D1/D5 receptor‐mediated dopamine effects on LTP may be higher in VH than DH and that VH may be specialized to acquire information about behaviorally relevant strong stimuli signaled by the dopamine system.     

Increased stress and smaller anterior hippocampal volume

Animal studies indicate that stress negatively impacts hippocampal structure; little is known, however, regarding the relationship between stress and hippocampal morphology in healthy humans. Twenty-one healthy adults underwent structural magnetic resonance imaging examinations and completed the Derogatis Stress Profile. Greater psychological stress at the time of the scan correlated significantly and more strongly with anterior than posterior hippocampal volume. These findings suggest that psychological stress may be associated with structural alterations in the anterior hippocampal formation and that this relationship may differ along the rostrocaudal axis of the hippocampus. Our results may also have implications for neuropsychiatric disorders that have implicated stress and hippocampal abnormalities in their pathogenesis.     

Hippocampal hemispheric and long‐axis differentiation of stimulus content during episodic memory encoding and retrieval: An activation likelihood estimation meta‐analysis

While there is ample evidence that the hippocampus is functionally heterogeneous along its longitudinal axis, there is still no consensus regarding its exact organization. Whereas spatial memory tasks frequently engage the posterior hippocampus, the regions engaged during episodic memory are more varying and may depend on the specific nature of the stimuli. Here, we investigate the effect of stimulus content on the location of hippocampal recruitment during episodic memory encoding and retrieval of pictorial and verbal material with a meta‐analysis approach, using activation likelihood estimation and restricting the analysis to the hippocampus. Verbal material was associated with left‐lateralized anterior activation, compared to pictorial material that recruited a more posterior aspect of the hippocampus, primarily within the right hemisphere. This effect held for encoding of both single items and item–item associations but was less clear during retrieval. The findings lend further support to a functional subdivision of the hippocampus along its longitudinal axis and indicate that the content of episodic memories is one factor that determines the location of hippocampal recruitment. © 2015 Wiley Periodicals, Inc.     

Region‐dependent and stage‐specific effects of stress,environmental enrichment,and antidepressant treatment on hippocampal neurogenesis

Chronic stress and depression are associated with decreased levels of hippocampal neurogenesis. On the other hand, antidepressants as well as environmental enrichment may rely in part on their pro‐neurogenic effects to improve cognition and mood. Because a functional heterogeneity has been consistently reported along the septo‐temporal axis of the hippocampus, regional changes in neurogenesis could differentially contribute to these effects and affect distinct hippocampal functions. Mapping these regional changes could therefore provide a better understanding of the function of newborn neurons. While some studies report region‐specific effects of stress and antidepressants on neurogenesis, it is unclear whether these changes affect distinct populations of newborn neurons according to their developmental stage in a region‐specific manner. By using endogenous markers and BrdU labeling we quantified the regional changes in cell proliferation and survival as well as in the number of neuronal progenitors and immature neurons following unpredictable chronic mild stress (UCMS), environmental enrichment (EE) and chronic fluoxetine (20 mg/kg/day) treatment along the septo‐temporal axis of the hippocampus. EE promoted cell proliferation and survival of 4‐week‐old newborn cells as well as increased the number and proportion of post‐mitotic immature neurons specifically within the septal hippocampus. By contrast, UCMS uniformly decreased cell proliferation, survival and immature newborn neurons but differentially affected progenitor cells with a decrease restricted to the temporal regions of the hippocampus. Whereas fluoxetine treatment in control mice affected proliferation and survival specifically in the temporal hippocampus, it reversed most of the UCMS‐induced alterations all along the septo‐temporal axis. These results highlight that different factors known for exerting a mood improving effect differentially regulate neurogenesis along the septo‐temporal axis of the hippocampus. Such region and stage specific effects may correlate to distinct functional properties of newborn neurons along the septo‐temporal axis of the hippocampus which may contribute differently to the pathophysiology of affective disorders. © 2013 Wiley Periodicals, Inc.     

The α5GABAA receptor modulates the induction of long‐term potentiation at ventral but not dorsal CA1 hippocampal synapses

The hippocampal synapses display conspicuous ability for long‐term plasticity which is thought to underlie learning and memory. Growing evidence shows that this ability differs along the long axis of the hippocampus, with the ventral CA1 hippocampal synapses displaying remarkably lower ability for long‐term potentiation (LTP) compared with their dorsal counterpart when activated with high‐frequency stimulation. Here, we show that low frequency, 10 Hz stimulation induced LTP more reliably in dorsal than in ventral CA1 field. Blockade of alpha5 subunit‐containing GABA_A receptors eliminated the difference between dorsal and ventral hippocampus. We propose that α5GABA_A receptor‐mediated activity plays a crucial role in regulating the threshold for induction of LTP especially at the ventral CA1 hippocampal synapses. This might have important implications for the functional specialization along the hippocampus. Synapse, 2014. © 2014 Wiley Periodicals, Inc.     

Mapping the electrophysiological and morphological properties of CA1 pyramidal neurons along the longitudinal hippocampal axis

Differences in behavioral roles, anatomical connectivity, and gene expression patterns in the dorsal, intermediate, and ventral regions of the hippocampus are well characterized. Relatively fewer studies have, however, focused on comparing the physiological properties of neurons located at different dorsoventral extents of the hippocampus. Recently, we reported that dorsal CA1 neurons are less excitable than ventral neurons. There is little or no information for how neurons in the intermediate hippocampus compare to those from the dorsal and ventral ends. Also, it is not known whether the transition of properties along the dorsoventral axis is gradual or segmented. In this study, we developed a statistical model to predict the dorsoventral position of transverse hippocampal slices. Using current clamp recordings combined with this model, we found that CA1 neurons in dorsal, intermediate, and ventral hippocampus have distinct electrophysiological and morphological properties and that the transition in most (but not all) of these properties from the ventral to dorsal end is gradual. Using linear and segmented regression analyses, we found that input resistance and resting membrane potential changed linearly along the V–D axis. Interestingly, the transition in resonance frequency, rebound slope, dendritic branching in stratum radiatum, and action potential properties was segmented along the V–D axis. Together, the findings from this study highlight the heterogeneity in CA1 neuronal properties along the entire longitudinal axis of hippocampus. © 2015 Wiley Periodicals, Inc.     

Ischemic LTP: NMDA‐dependency and dorso/ventral distribution within the hippocampus

A transient ischemic episode causes a reduction in evoked EPSPs in hippocampal slices, followed by an NMDA dependent LTP. We explored the relations between ischemic LTP (iLTP) and the more conventional tetanic LTP (tLTP) in CA1 region of slices along the dorsal/ventral axis of the hippocampus. Dorsal hippocampal (DH) slices produced a much larger iLTP than their ventral hippocampal (VH) counterparts. In both regions, iLTP and tLTP shared the same NMDA mediated potentiation, such that one LTP saturated the ability of the other treatment to generate LTP. The smaller LTP in VH was correlated with a lower NMDA‐mediated EPSP, and a parallel lower density of NMDA receptors. Calcium permeable AMPA receptors did not contribute to the DH/VH disparity. We conclude that a differential distribution of NMDA receptor subunits along the septotemporal axis of the hippocampus controls the diverse ability to evoke iLTP and tLTP in the two regions and may underlie their characteristic behavioral outputs as well as their differential sensitivity to ischemia. © 2015 Wiley Periodicals, Inc.     

Self-motion and the origin of differential spatial scaling along the septo-temporal axis of the hippocampus

Spatial scaling of place specific activity in the hippocampus varies systematically from the septal pole (high resolution) to the temporal pole (low resolution). Place fields get progressively larger, and the probability of observing a field in a given environment gets progressively smaller. It was previously found that decoupling movement in space from ambulation, by having the animal actively ride on a mobile platform, results in marked enlargement of the spatial scale factor in the dorsal hippocampus and a reduction in the increase in theta rhythm power with running speed, suggesting that a self-motion signal determines the spatial scale at which the hippocampal population vector updates. These results led to the hypothesis that the gain of the self-motion signal may vary systematically along the septo-temporal axis of the hippocampus. To test this hypothesis, EEG theta rhythm and ensembles of CA1 pyramidal cells and interneurons were recorded from the extreme dorsal and middle portions of the hippocampus. Pyramidal cell population vectors representing successive locations became decorrelated over substantially shorter distances in the dorsal than in the middle hippocampus. Dorsal pyramidal cells had smaller place fields, higher mean and peak firing rates, and higher intrinsic oscillation frequencies during track running than that of middle pyramidal cells. Both dorsal pyramidal cells and interneurons had more elevated mean rates during running, compared with rest, than that of the corresponding cell classes in the middle hippocampus, and both cell classes increased their rates more as a function of speed in the dorsal hippocampus.The amplitude, but not the frequency of fissure recorded theta rhythm, increased more as a function of running speed in the dorsal than in the middle hippocampus. We conclude that variation in the neuronal response to movement speed is the likely basis for the systematic variation in spatial scaling along the septo-temporal axis of the hippocampus.     

Laminar origin and septotemporal distribution of entorhinal and perirhinal projections to the hippocampus in the cat

The Projections o the entorhinal and perirhinal cortices to the hippocampus in the cat have been studied with retrograde and anterograde tracing techniques. Retarogradely transported tracers, which were injected at different levels along the septotemporal longitudinal hippocampal axis, result in labeled neurons in superficial entorhinal cortical layers II and III. Occasionally, labeled cells were also observed in the deepest entorhinal layer as well as in the superficial layers of the perirhinal area 35. It could further be shown that labeled neurons located superficially in the entorhinal cortex corresponds to a septotemporal gradient along the longitudinal axis of the hippocampus. This topographical organization of the entorhinal-hippocampal projection system could be substantiated by the use of anterograde tracing of radioactively labeled amino acids. Injections in the entorhinal cortex produce labeled fibers in the hippocampus. Injections in the perirhinal area 35 result also in labeling over the hippocampus, whereas area 36 does not seem to distribute fibers to the hippocampus. As anticipated from the results of the retrograde tracing experiments, injections located laterally, in or close to the posterior rhinal sulcus, produce prominent labeling over the septal pole of the hippocampus, whereas progressively more medially located injections result in progressively more temporally located labeling. This topographical distribution of perforant path fibers along the septotemporal axis of the hippocampus, which is related to a lateromedial axis in the entorhinal cortex, has been observed following injections in the lateral entorhinal area (LEA) as well as in the medial entorhinal area (MEA). The present observations are discussed in regard of other connectional and putative functional differences between the septal and temporal hippocampus.