Though it has been known for over half a century that interference with the normal activity of septohippocampal neurons can abolish hippocampal theta rhythmicity, a definitive answer to the question of its function has remained elusive. To clarify the role of septal circuits and theta in location specific activity of place cells and spatial behavior, three drugs were delivered to the medial septum of rats: tetracaine, a local anesthetic; muscimol, a GABA-A agonist; and gabazine, a GABA-A antagonist. All three drugs disrupted normal oscillatory activity in the hippocampus. However, tetracaine and muscimol both reduced spatial firing and interfered with the rat’s ability to navigate to a hidden goal. After gabazine, location specific firing was preserved in the absence of theta, but rats were unable to accurately locate the hidden goal. These results indicate that theta is unnecessary for location specific firing of hippocampal cells, and that place cell activity cannot support accurate navigation when septal circuits are disrupted.

The fundamental property of topological dimension of neural activity has never been measured before. We measured the topological dimension of the activity of 89 rat hippocampal place cells recorded during foraging using the neighborhood boundary countdown method. Points were rate vectors forming a manifold in an 89 dimensional rate space Since a boundary has one less dimension than the neighborhood it encloses, reducing the dimension in sequential radial cuts finally arrives at boundary that is two points. The number of cuts required is the topological dimension of the set. Due to sparsity, we used a shell-like boundary with thickness. As expected, we found the large inductive dimension of this set of points to be two. To examine the robustness of the method, we used both real and modeled place cells and varied the number of neurons, duration of the time step and smoothing, radius and thickness for the boundary, decrement of the radius with each cut, requirements for the center point, and number of points in the final cluster. With the exception of shell thickness, the result was insensitive to these variations. Knowing the topological dimension allows application of rigorous topological principles to the activity of neuron populations. The method potentially can be applied to other neural classes and other behaviors, to enumerate firing variables when they are unknown, even count the factors influencing neural activity in sleep.

The medial entorhinal cortex, populated by grid cells, projects both directly and indirectly to the CA1 and CA3 cortices, the sites of hippocampal place cells. The study by Ormond and McNaughton (1) investigates a potential mechanism by which grid cells of the medial entorhinal cortex (MEC) exert their influence on the formation of firing fields of place cells. Specifically, the authors propose a “Fourier hypothesis” by which the spatial frequencies from several grid cell modules converge on the place-cell layer, molding the contours of firing fields to a composite of those several frequencies; Ormond and McNaughton tested the theory by inactivating specific input components and obtained fascinating results, largely supporting the model.

Recent interest in the neural bases of spatial navigation stems from the discovery of neuronal populations with strong, specific spatial signals. The regular firing field arrays of medial entorhinal grid cells suggest that they may provide place cells with distance information extracted from the animal's self-motion, a notion we critically review by citing new contrary evidence. Next, we question the idea that grid cells provide a rigid distance metric. We also discuss evidence that normal navigation is possible using only landmarks, without self-motion signals. We then propose a model that supposes that information flow in the navigational system changes between light and dark conditions. We assume that the true map-like representation is hippocampal and argue that grid cells have a crucial navigational role only in the dark. In this view, their activity in the light is predominantly shaped by landmarks rather than self-motion information, and so follows place cell activity; in the dark, their activity is determined by self-motion cues and controls place cell activity. A corollary is that place cell activity in the light depends on non-grid cells in ventral medial entorhinal cortex. We conclude that analysing navigational system changes between landmark and no-landmark conditions will reveal key functional properties.

While extracellular somatic action potentials from freely moving rats have been well characterized, axonal activity has not. We report direct extracellular tetrode recordings of putative axons whose principal feature is a short duration waveform (SDW) with an average peak-trough length less than 179 μs. While SDW recordings using tetrodes have previously been treated as questionable or classified as cells, we hypothesize that they are representative of axonal activity. These waveforms have significantly shorter duration than somatic action potentials, are triphasic and are therefore similar to classic descriptions of microelectrode recordings in white matter and of in vitro action potential propagation along axons. We describe SDWs recorded from pure white-matter tracts including the alveus and corpus callosum. Recordings of several SDWs in the alveus exhibit grid-like firing patterns suggesting these axons carry spatial information from entorhinal cortical neurons. Finally, we locally injected the GABAA agonist Muscimol into layer CA1 of the hippocampus while simultaneously recording somatic activity and SDWs on the same tetrodes. The persistent activity of SDWs during Muscimol inactivation of somatic action potentials indicates that SDWs are representative of action potential propagation along axons projecting from more distal somata. This characterization is important as it illustrates the dangers of exclusively using spike duration as the sole determinant of unit type, particularly in the case of interneurons whose peak-trough times overlap with SDWs. It may also allow future studies to explore how axonal projections from disparate brain regions integrate spatial information in the hippocampus, and provide a basis for studying the effects of pharmaceutical agents on signal transmission in axons, and ultimately to aid in defining the potential role of axons in cognition.

Repetitive one-per-day seizures induced in otherwise normal rats by the volatile convulsant flurothyl decrease the accuracy of locating a hidden goal without changing the mean location of goal selection. We now show that an 8-d series of such seizures degrades the spatial signal carried by the firing of hippocampal pyramidal cells and specifically reduces the information conveyed by the place cell subset of pyramidal cells. This degradation and a concomitant slowing of the hippocampal theta rhythm occur over time courses parallel to the development of the behavioral deficit and plausibly account for the impairment. The details of how pyramidal cell discharge weakens are, however, unexpected. Rather than a reduction in the precision of location-specific firing distributed evenly over all place cells, the number of place cells decreases with seizure number, although the remaining place cells remain quite intact. Thus, with serial seizures there is a cell-specific conversion of robust place cells to sporadically firing (<0.1 spike/s) “low-rate” cells as opposed to gradual loss of place cell resolution. This transformation occurs in the absence of significant changes in the discharge rate of hippocampal interneurons, suggesting that the decline in the number of place cells is not a simple matter of increased inhibitory tone. The cumulative transformation of place cells to low-rate cells by repetitive seizures may reflect a homeostatic, negative-feedback process.

It is widely held that spatial computations in the rodent hippocampus require the location-specific discharge of place cells that together form a stable cognitive map used to solve and perform spatial tasks. It is not known, however, if map stability requires persistent hippocampal synaptic strength changes that are vulnerable to blockade of protein kinase Mζ (PKMζ) phosphorylation activity, a manipulation that reverses hippocampal LTP and disrupts multiple forms of long-term memory. Here we report that acute intrahippocampal inhibition of PKMζ disrupts place cell activity in a familiar environment, where the map is expected to be stable. After this disruption, new, stable spatial firing patterns can later form, but the new and original maps are unrelated even though the rat is exposed to a constant environment. We therefore propose that the previously demonstrated erasure of stored spatial memory and the disruption of place cell firing are parallel effects of PKMζ blockade. We similarly propose that the known sparing of new spatial memory formation depends on the sparing of new map formation. On these bases, we argue that the loss of the map used to perform a practiced spatial task leads to behavioral performance deficits, and that synaptic plasticity maintained by PKMζ, which stabilizes the map, is essential for the proper expression of spatial memory.

We compared the spatial firing properties of hippocampal place cells as a hungry rat foraged for randomly scattered food pellets in a familiar environment while it was by itself and while it shared the arena with a second rat that also was trained in the same task. Our goal was to determine if the hippocampal mapping system remained functional in the presence of the second rat, despite a strong initial tendency of the two animals to stay close together and despite the increased complexity of the sensory surroundings. We found that almost all place cell firing fields were only marginally changed by introducing the second rat. In particular, there was no evidence of the remapping characteristic of place cells in a sufficiently different novel environment. Instead, firing fields became somewhat less well organized and slightly weaker in the presence of the second rat. These second order changes were found to be distance dependent; the degradation of firing properties was maximal when the two rats were near each other. We conclude that signals in the hippocampal mapping system are affected to a small enough extent that accurate navigational is still possible when the environment is enriched in this realistic fashion. © 2011 Wiley Periodicals, Inc.