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William E Skaggs

Publications and source records attributed to William E Skaggs.

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Deforming the hippocampal map.

To investigate conjoint stimulus control over place cells, Fenton et al. (J Gen Physiol 116:191-209, 2000a) recorded while rats foraged in a cylinder with 45 degrees black and white cue cards on the wall. Card centers were 135 degrees apart. In probe trials, the cards were rotated together or apart by 25 degrees . Firing field centers shifted during these trials, stretching and shrinking the cognitive map. Fenton et al. (2000b) described this deformation with an ad hoc vector field equation. We consider what sorts of neural network mechanisms might be capable of accounting for their observations. In an abstract, maximum likelihood formulation, the rat's location is estimated by a conjoint probability density function of landmark positions. In an attractor neural network model, recurrent connections produce a bump of activity over a two-dimensional array of cells; the bump's position is influenced by landmark features such as distances or bearings. If features are chosen with appropriate care, the attractor network and maximum likelihood models yield similar results, in accord with previous demonstrations that recurrent neural networks can efficiently implement maximum likelihood computations (Pouget et al. Neural Comput 10:373-401, 1998; Deneve et al. Nat Neurosci 4:826-831, 2001).

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Hippocampal place cells are not controlled by visual input during the small irregular activity state in the rat.

In the actively foraging rat, hippocampal pyramidal cells have strong spatial correlates. Each "place cell" fires rapidly only when the rat enters a particular delimited portion of its environment, called the "place field" of that cell. Hippocampal pyramidal cells also exhibit spatial selectivity during a physiological state that occurs during sleep, termed "small irregular activity" (SIA), because of the appearance of the hippocampal EEG. It is not known whether rats determine their current location in space during SIA using current visual information or whether they recall the location in which they fell asleep. To address this question, we recorded spikes from ensembles of CA1 pyramidal cells and hippocampal EEG while rats slept along the edge of a large circular recording arena with minimal local features in a room with prominent distal visual cues. To move the rats to a new location in the room while they were sleeping, we slowly rotated the recording arena on which they slept to a new orientation in the room. Hippocampal place cell activity in subsequent SIA episodes reflected the location in the room in which the rats fell asleep, rather than the location to which they were moved, although the alignment of the rats' spatial map was governed by the room cues in the subsequent active foraging session. Thus, the hippocampal population activity during SIA does not result from the processing of current visual information but instead probably reflects a memory for the location in which the rat fell asleep.

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Level of arousal during the small irregular activity state in the rat hippocampal EEG.

The sleeping rat cycles between two well-characterized hippocampal physiological states, large irregular activity (LIA) during slow-wave sleep (SWS) and theta activity during rapid-eye-movement sleep (REM). A third, less well-characterized electroencephalographic (EEG) state, termed "small irregular activity" (SIA), has been reported to occur when an animal is startled out of sleep without moving and during active waking when it abruptly freezes. We recently found that the hippocampal population activity of a spontaneous sleep state whose EEG resembles SIA reflects the rat's current location in space, suggesting that it is also a state of heightened arousal. To test whether this spontaneous SIA state corresponds to the SIA state reported in the literature and to compare the level of arousal during SIA to the other well-characterized physiological states, we recorded unit activity from ensembles of hippocampal CA1 pyramidal cells, EEG from the hippocampus and the neocortex, and electromyography (EMG) from the dorsal neck musculature in rats presented with auditory stimuli while foraging for randomly scattered food pellets and while sleeping. Auditory stimuli presented during sleep reliably induced SIA episodes very similar to spontaneous SIA in hippocampal and neocortical EEG amplitudes and power spectra, EMG amplitude, and CA1 population activity. Both spontaneous and elicited SIA exhibited neocortical desynchronization, and both had EMG amplitude comparable to that of waking LIA. We conclude based on this and other evidence that spontaneous SIA and elicited SIA correspond to a single state and that the level of arousal in SIA is higher than in the well-characterized sleep states but lower than the active theta state.

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Hippocampal population activity during the small-amplitude irregular activity state in the rat.

The sleeping rat cycles between two well-characterized physiological states, slow-wave sleep (SWS) and rapid-eye-movement sleep (REM), often identified by the presence of large-amplitude irregular activity (LIA) and theta activity, respectively, in the hippocampal EEG. Inspection of the activity of ensembles of hippocampal CA1 complex-spike cells along with the EEG reveals the presence of a third physiological state within SWS. We characterize the hippocampal EEG and population activity of this third state relative to theta activity and LIA, its incidence relative to REM and LIA, and the functional correlates of its population activity. This state occurs repeatedly within stretches of SWS, occupying approximately 33% of SWS and approximately 20% of total sleep, and it follows nearly every REM episode; however, it never occurs just before a REM episode. The EEG during this state becomes low in amplitude for a few seconds, probably corresponding to "small-amplitude irregular activity" (SIA) described in the literature; we will call its manifestation during sleep "S-SIA." During S-SIA, a small subset of cells becomes active, whereas the rest remain nearly silent, with the same subset of cells active across long sequences of S-SIA episodes. These cells are physiologically indistinguishable from ordinary complex-spike cells; thus, the question arises as to whether they have any special functional correlates. Indeed, many of these cells are found to have place fields encompassing the location where the rat sleeps, raising the possibility that S-SIA is a state of increased alertness in which the animal's location in the environment is represented in the brain.

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Concordant and discordant coding of spatial location in populations of hippocampal CA1 pyramidal cells.

Pyramidal cells in the rat hippocampus commonly show place-related activity, but it has been difficult to understand the factors that govern them. A particularly important question is whether individual cells have identifiable correlates that can be manipulated independently of the correlates of other cells. Recently Tanila et al. examined the activity of small ensembles of hippocampal cells in rats running on a plus-maze with distinct intra- and extramaze cues. When the two sets of cues were rotated 90 degrees in opposite directions, some cells followed the intramaze cues, others followed the extramaze cues, and others "remapped" unpredictably; moreover, all possible combinations were seen within simultaneously recorded ensembles. In the current study, CA1 pyramidal cell population activity was recorded from four rats in a similar paradigm, using a recording system that permitted the analysis of ensembles of 4-70 simultaneously recorded units. The results were consistent with the data from the earlier study in showing an increase in remapping over time and in showing some place fields following one of the defined sets of cues while others remapped. When the possibility of random remapping was controlled for, however, the analysis did not show significant numbers of place fields following both sets of cues simultaneously. Furthermore, all rats initially showed fully concordant responses with all place fields following the local cues. For two rats, this pattern continued until a new configuration was introduced at which time all fields switched to follow the distal cues. Taken together, the results are difficult to reconcile with the hypothesis that individual hippocampal cells encode information about different subsets of cues in the environment.

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