Since the first place cell was recorded and the cognitive-map theory was subsequently formulated, investigation of spatial representation in the hippocampal formation has evolved in stages. Early ...studies sought to verify the spatial nature of place cell activity and determine its sensory origin. A new epoch started with the discovery of head direction cells and the realization of the importance of angular and linear movement-integration in generating spatial maps. A third epoch began when investigators turned their attention to the entorhinal cortex, which led to the discovery of grid cells and border cells. This review will show how ideas about integration of self-motion cues have shaped our understanding of spatial representation in hippocampal-entorhinal systems from the 1970s until today. It is now possible to investigate how specialized cell types of these systems work together, and spatial mapping may become one of the first cognitive functions to be understood in mechanistic detail.
Grid cells in the medial entorhinal cortex have spatial firing fields that repeat periodically in a hexagonal pattern. When animals move, activity is translated between grid cells in accordance with ...the animal's displacement in the environment. For this translation to occur, grid cells must have continuous access to information about instantaneous running speed. However, a powerful entorhinal speed signal has not been identified. Here we show that running speed is represented in the firing rate of a ubiquitous but functionally dedicated population of entorhinal neurons distinct from other cell populations of the local circuit, such as grid, head-direction and border cells. These 'speed cells' are characterized by a context-invariant positive, linear response to running speed, and share with grid cells a prospective bias of ∼50-80 ms. Our observations point to speed cells as a key component of the dynamic representation of self-location in the medial entorhinal cortex.
Theories on the functions of the hippocampal system are based largely on two fundamental discoveries: the amnestic consequences of removing the hippocampus and associated structures in the famous ...patient H.M. and the observation that spiking activity of hippocampal neurons is associated with the spatial position of the rat. In the footsteps of these discoveries, many attempts were made to reconcile these seemingly disparate functions. Here we propose that mechanisms of memory and planning have evolved from mechanisms of navigation in the physical world and hypothesize that the neuronal algorithms underlying navigation in real and mental space are fundamentally the same. We review experimental data in support of this hypothesis and discuss how specific firing patterns and oscillatory dynamics in the entorhinal cortex and hippocampus can support both navigation and memory.
The encoding of time and its binding to events are crucial for episodic memory, but how these processes are carried out in hippocampal-entorhinal circuits is unclear. Here we show in freely foraging ...rats that temporal information is robustly encoded across time scales from seconds to hours within the overall population state of the lateral entorhinal cortex. Similarly pronounced encoding of time was not present in the medial entorhinal cortex or in hippocampal areas CA3-CA1. When animals' experiences were constrained by behavioural tasks to become similar across repeated trials, the encoding of temporal flow across trials was reduced, whereas the encoding of time relative to the start of trials was improved. The findings suggest that populations of lateral entorhinal cortex neurons represent time inherently through the encoding of experience. This representation of episodic time may be integrated with spatial inputs from the medial entorhinal cortex in the hippocampus, allowing the hippocampus to store a unified representation of what, where and when.
Accumulating evidence points to cortical oscillations as a mechanism for mediating interactions among functionally specialized neurons in distributed brain circuits. A brain function that may use ...such interactions is declarative memory--that is, memory that can be consciously recalled, such as episodes and facts. Declarative memory is enabled by circuits in the entorhinal cortex that interface the hippocampus with the neocortex. During encoding and retrieval of declarative memories, entorhinal and hippocampal circuits are thought to interact via theta and gamma oscillations, which in awake rodents predominate frequency spectra in both regions. In favour of this idea, theta-gamma coupling has been observed between entorhinal cortex and hippocampus under steady-state conditions in well-trained rats; however, the relationship between interregional coupling and memory formation remains poorly understood. Here we show, by multisite recording at successive stages of associative learning, that the coherence of firing patterns in directly connected entorhinal-hippocampus circuits evolves as rats learn to use an odour cue to guide navigational behaviour, and that such coherence is invariably linked to the development of ensemble representations for unique trial outcomes in each area. Entorhinal-hippocampal coupling was observed specifically in the 20-40-hertz frequency band and specifically between the distal part of hippocampal area CA1 and the lateral part of entorhinal cortex, the subfields that receive the predominant olfactory input to the hippocampal region. Collectively, the results identify 20-40-hertz oscillations as a mechanism for synchronizing evolving representations in dispersed neural circuits during encoding and retrieval of olfactory-spatial associative memory.
We developed a miniaturized two-photon microscope (MINI2P) for fast, high-resolution, multiplane calcium imaging of over 1,000 neurons at a time in freely moving mice. With a microscope weight below ...3 g and a highly flexible connection cable, MINI2P allowed stable imaging with no impediment of behavior in a variety of assays compared to untethered, unimplanted animals. The improved cell yield was achieved through a optical system design featuring an enlarged field of view (FOV) and a microtunable lens with increased z-scanning range and speed that allows fast and stable imaging of multiple interleaved planes, as well as 3D functional imaging. Successive imaging across multiple, adjacent FOVs enabled recordings from more than 10,000 neurons in the same animal. Large-scale proof-of-principle data were obtained from cell populations in visual cortex, medial entorhinal cortex, and hippocampus, revealing spatial tuning of cells in all areas.
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•We made a light-weight 2-photon miniscope for calcium imaging in freely moving mice•Stable high-quality imaging was observed during a wide spectrum of behaviors•Activity can be monitored in volumes of over 1,000 visual or entorhinal-cortex cells•A custom-designed z-scanning module allows fast imaging across multiple planes
Development of a miniature 2-photon miniscope for large-scale calcium imaging in freely moving mice allows stable simultaneous recording of more than a thousand cells across multiple planes of densely active cortical regions in a wide spectrum of behavioral tasks without impediment of the animal's behavior.
Ten Years of Grid Cells Rowland, David C; Roudi, Yasser; Moser, May-Britt ...
Annual review of neuroscience,
07/2016, Letnik:
39, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The medial entorhinal cortex (MEC) creates a neural representation of space through a set of functionally dedicated cell types: grid cells, border cells, head direction cells, and speed cells. Grid ...cells, the most abundant functional cell type in the MEC, have hexagonally arranged firing fields that tile the surface of the environment. These cells were discovered only in 2005, but after 10 years of investigation, we are beginning to understand how they are organized in the MEC network, how their periodic firing fields might be generated, how they are shaped by properties of the environment, and how they interact with the rest of the MEC network. The aim of this review is to summarize what we know about grid cells and point out where our knowledge is still incomplete.
Grid cells are neurons with periodic spatial receptive fields (grids) that tile two-dimensional space in a hexagonal pattern. To provide useful information about location, grids must be stably ...anchored to an external reference frame. The mechanisms underlying this anchoring process have remained elusive. Here we show in differently sized familiar square enclosures that the axes of the grids are offset from the walls by an angle that minimizes symmetry with the borders of the environment. This rotational offset is invariably accompanied by an elliptic distortion of the grid pattern. Reversing the ellipticity analytically by a shearing transformation removes the angular offset. This, together with the near-absence of rotation in novel environments, suggests that the rotation emerges through non-coaxial strain as a function of experience. The systematic relationship between rotation and distortion of the grid pattern points to shear forces arising from anchoring to specific geometric reference points as key elements of the mechanism for alignment of grid patterns to the external world.
More than three decades of research have demonstrated a role for hippocampal place cells in representation of the spatial environment in the brain. New studies have shown that place cells are part of ...a broader circuit for dynamic representation of self-location. A key component of this network is the entorhinal grid cells, which, by virtue of their tessellating firing fields, may provide the elements of a path integration-based neural map. Here we review how place cells and grid cells may form the basis for quantitative spatiotemporal representation of places, routes, and associated experiences during behavior and in memory. Because these cell types have some of the most conspicuous behavioral correlates among neurons in nonsensory cortical systems, and because their spatial firing structure reflects computations internally in the system, studies of entorhinal-hippocampal representations may offer considerable insight into general principles of cortical network dynamics.
A growing body of evidence suggests that memories are stored in the hippocampus by integrating spatial information from specialized cell types in the medial entorhinal cortex (MEC) with nonspatial ...information from cells in the lateral entorhinal cortex (LEC) 1–5. LEC neurons show little spatial modulation when rats run in empty open-field environments 6, 7 but fire in the vicinity of discrete objects 7, suggesting that they provide information about the specific content of the spatial environment. It is unclear, however, whether firing at objects is elicited purely by stimulus properties, in a sensory-like manner, or whether any higher-order property, such as the history of experience, is also relevant. To address this question, we recorded from LEC neurons in an open field where objects were present on a subset of the trials. Whereas some neurons fired at the objects, other cells developed specific firing at places where objects had been located on previous trials, providing a readout of past experience in the environment. The latter cells generally did not respond to the object when it was present, suggesting that object cells and object-trace cells are independent cell classes. These findings identify LEC as a component of the hippocampal-cortical circuit for object-place memory.
► The lateral entorhinal cortex contains cells that fire at past object locations ► These trace cells do not respond to an object when the object is present ► Trace responses can be elicited at a variety of locations and by a variety of objects ► Trace cells provide a readout of past experience at specific locations
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