The hippocampus generates distinct neural codes to disambiguate similar experiences, a process thought to underlie episodic memory function. Entorhinal grid cells provide a prominent spatial signal ...to hippocampus, and changes in their firing pattern could thus generate a distinct spatial code in each context. We examined whether we would preclude the emergence of new spatial representations in a novel environment during muscimol inactivation of the medial septal area, a manipulation known to disrupt theta oscillations and grid cell firing. We found that new, highly distinct configurations of place fields emerged immediately and remained stable during the septal inactivation. The new place code persisted when theta oscillations had recovered. Theta rhythmicity and feedforward input from grid cell networks were thus not required to generate new spatial representations in the hippocampus.
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•Septal inactivation reduced theta power in hippocampus and entorhinal cortex•Theta power was reduced to levels that are known to disrupt entorhinal grid cells•Intact hippocampal place fields appear in a new room during the septal inactivation•The newly established place fields are retained after recovery from inactivation
Pharmacological inactivation of the medial septal area is known to disrupt the spatial firing patterns of grid cells. Brandon et al. demonstrate that hippocampal neurons generate distinct and stable spatial firing patterns in a novel room during septal inactivation.
The hippocampal CA2 subregion has a different anatomical connectivity pattern within the entorhino-hippocampal circuit than either the CA1 or CA3 subregion. Yet major differences in the neuronal ...activity patterns of CA2 compared with the other CA subregions have not been reported. We show that standard spatial and temporal firing patterns of individual hippocampal principal neurons in behaving rats, such as place fields, theta modulation, and phase precession, are also present in CA2, but that the CA2 subregion differs substantially from the other CA subregions in its population coding. CA2 ensembles do not show a persistent code for space or for differences in context. Rather, CA2 activity patterns become progressively dissimilar over time periods of hours to days. The weak coding for a particular context is consistent with recent behavioral evidence that CA2 circuits preferentially support social, emotional, and temporal rather than spatial aspects of memory.
The entorhinal cortex provides the primary cortical projections to the hippocampus, a brain structure critical for memory. However, it remains unclear how the precise firing patterns of medial ...entorhinal cortex (MEC) cells influence hippocampal physiology and hippocampus-dependent behavior. We found that complete bilateral lesions of the MEC resulted in a lower proportion of active hippocampal cells. The remaining active cells had place fields, but with decreased spatial precision and decreased long-term spatial stability. In addition, MEC rats were as impaired in the water maze as hippocampus rats, while rats with combined MEC and hippocampal lesions had an even greater deficit. However, MEC rats were not impaired on other hippocampus-dependent tasks, including those in which an object location or context was remembered. Thus, the MEC is not necessary for all types of spatial coding or for all types of hippocampus-dependent memory, but it is necessary for the normal acquisition of place memory.
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•Hippocampal place cells form without input from the medial entorhinal cortex•MEC lesions disrupt place cell precision and stability•MEC lesions impair a flexible type of place memory that involves navigation•MEC lesions spare other hippocampus-dependent spatial memory
To address whether the medial entorhinal cortex (MEC) is necessary for spatial coding and hippocampus-dependent memory, Hales et al. selectively removed the entire MEC in rats. This led to only partial deterioration of hippocampal spatial coding, and the MEC was found to be necessary for only a limited number of hippocampus-dependent memory tasks.
Highlights • The firing location of place cells does not change when grid firing patterns are altered. • New and distinct spatial maps emerge without grid cell inputs. • Hippocampal spatial firing is ...partially retained without medial entorhinal cortex inputs. • Medial entorhinal circuits for spatial and for memory computations may be distinct.
Theoretical models have long pointed to the dentate gyrus as a possible source of neuronal pattern separation. In agreement with predictions from these models, we show that minimal changes in the ...shape of the environment in which rats are exploring can substantially alter correlated activity patterns among place-modulated granule cells in the dentate gyrus. When the environments are made more different, new cell populations are recruited in CA3 but not in the dentate gyrus. These results imply a dual mechanism for pattern separation in which signals from the entorhinal cortex can be decorrelated both by changes in coincidence patterns in the dentate gyrus and by recruitment of nonoverlapping cell assemblies in CA3.
Complex spatial working memory tasks have been shown to require both hippocampal sharp-wave ripple (SWR) activity and dentate gyrus (DG) neuronal activity. We therefore asked whether DG inputs to CA3 ...contribute to spatial working memory by promoting SWR generation. Recordings from DG and CA3 while rats performed a dentate-dependent working memory task on an eight-arm radial maze revealed that the activity of dentate neurons and the incidence rate of SWRs both increased during reward consumption. We then found reduced reward-related CA3 SWR generation without direct input from dentate granule neurons. Furthermore, CA3 cells with place fields in not-yet-visited arms preferentially fired during SWRs at reward locations, and these prospective CA3 firing patterns were more pronounced for correct trials and were dentate-dependent. These results indicate that coordination of CA3 neuronal activity patterns by DG is necessary for the generation of neuronal firing patterns that support goal-directed behavior and memory.
Neuronal code for extended time in the hippocampus Mankin, Emily A; Sparks, Fraser T; Slayyeh, Begum ...
Proceedings of the National Academy of Sciences,
11/2012, Letnik:
109, Številka:
47
Journal Article
Recenzirano
Odprti dostop
The time when an event occurs can become part of autobiographical memories. In brain structures that support such memories, a neural code should exist that represents when or how long ago events ...occurred. Here we describe a neuronal coding mechanism in hippocampus that can be used to represent the recency of an experience over intervals of hours to days. When the same event is repeated after such time periods, the activity patterns of hippocampal CA1 cell populations progressively differ with increasing temporal distances. Coding for space and context is nonetheless preserved. Compared with CA1, the firing patterns of hippocampal CA3 cell populations are highly reproducible, irrespective of the time interval, and thus provide a stable memory code over time. Therefore, the neuronal activity patterns in CA1 but not CA3 include a code that can be used to distinguish between time intervals on an extended scale, consistent with behavioral studies showing that the CA1 area is selectively required for temporal coding over such periods.
The medial entorhinal cortex (mEC) has been identified as a hub for spatial information processing by the discovery of grid, border, and head-direction cells. Here we find that in addition to these ...well-characterized classes, nearly all of the remaining two-thirds of mEC cells can be categorized as spatially selective. We refer to these cells as nongrid spatial cells and confirmed that their spatial firing patterns were unrelated to running speed and highly reproducible within the same environment. However, in response to manipulations of environmental features, such as box shape or box color, nongrid spatial cells completely reorganized their spatial firing patterns. At the same time, grid cells retained their spatial alignment and predominantly responded with redistributed firing rates across their grid fields. Thus, mEC contains a joint representation of both spatial and environmental feature content, with specialized cell types showing different types of integrated coding of multimodal information.
•Nearly all principal cells in mEC exhibit spatial coding properties•Nongrid spatial cell firing is consistent within the same environment•Grid cell firing rates redistribute across fields in response to box manipulations•Nongrid spatial cells respond to box manipulations with reorganized spatial firing
Diehl et al. describe how grid and nongrid spatial cells can represent environmental features, such as shape or color. Grid cells retain stable spatial representations but show rate differences across fields, while nongrid spatial cells profoundly alter their spatial firing.
Grid cells in parahippocampal cortices fire at vertices of a periodic triangular grid that spans the entire recording environment. Such precise neural computations in space have been proposed to ...emerge from equally precise temporal oscillations within cells or within the local neural circuitry. We found that grid-like firing patterns in the entorhinal cortex vanished when theta oscillations were reduced after intraseptal lidocaine infusions in rats. Other spatially modulated cells in the same cortical region and place cells in the hippocampus retained their spatial firing patterns to a larger extent during these periods without well-organized oscillatory neuronal activity. Precisely timed neural activity within single cells or local networks is thus required for periodic spatial firing but not for single place fields.
In epilepsy, brain networks generate pathological high-frequency oscillations (pHFOs) during interictal periods. To understand how pHFOs differ from normal oscillations in overlapping frequency bands ...and potentially perturb hippocampal processing, we performed high-density single unit and local field potential recordings from hippocampi of behaving rats with and without chronic epilepsy. In epileptic animals, we observed two types of co-occurring fast oscillations, which by comparison to control animals we could classify as 'ripple-like' or 'pHFO'. We compared their spectral characteristics, brain state dependence, and cellular participants. Strikingly, pHFO occurred irrespective of brain state, were associated with interictal spikes, engaged distinct subnetworks of principal neurons compared to ripple-like events, increased the sparsity of network activity, and initiated both general and immediate disruptions in spatial information coding. Taken together, our findings suggest that events that result in pHFOs have an immediate impact on memory processes, corroborating the need for proper classification of pHFOs to facilitate therapeutic interventions that selectively target pathological activity.
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