Architecture of spatial circuits in the hippocampal region
The hippocampal region contains a diversity of neural circuits and functionally specialized cell types involved in the representation of self-location. Our understanding of the wiring between and within the different subregions that make up the hippocampal formation and the parahippocampal region has changed. Initially, the system appeared neatly organized, with individual functional cell-types belonging to unique neuronal networks, organized as a serial information processor. This has led to various attempts to causally relate network architecture within and between these unique circuits to functional outcome. In my presentation I will argue that the classic serial view no longer faithfully describes the organization of the region. I will focus on MEC, its intrinsic network and how this relates to the cortex on the one hand and the hippocampus on the other hand. Experimental data indicate that it is time to replace the serial concept with a complex combination of multiple parallel networks to which embedded feedback and feedforward connectivity needs to be added. Integrating specific local inhibitory networks will be the next step needed in order to fully grasp the potential functional complexity of the system.
Cathrin B Canto, Jonathan J Couey, Noriko Koganezawa, Kally C O’Reilly
Dr Colin Lever, University of Durham, UK
Development of the HF spatial system: grid, boundary, head direction and place cells
Dr Tom Wills, University College London, UK
In order to understand when and how the hippocampal neural representation of space is created during development, we recorded the activity of single neurons from awake and behaving pre-weanling rat pups from P12 onwards.
Confirming previous findings, we find that Head Direction Cells represent the earliest developing spatial signal, with stable Head Direction cells emerging in the dorsal pre-subiculum at P14. Several characteristics of both Head Direction and Grid cells’ firing indicate that an adult-like network is present soon after spatially-tuned firing is first observed. In particular, network behaviour consistent with continuous attractor models was present from the earliest ages that spatial firing could be detected.
By contrast, we find that Place Cell firing matures gradually. Although adult-like place cells can be seen at P14, the CA1 network is not fully mature until several weeks of age. What are the inputs that support Place Cell firing in the youngest animals? We find evidence that, as for adults, place fields are bound to configurations of multiple cues, and that the geometry of environmental boundaries may be one of the earliest spatial features capable of stabilising Place Cell responses.
Engrams for genuine and false memories
Professor Susumu Tonegawa, RIKEN-MIT Center at the Picower Institute, MIT, USA
An important question in neuroscience is how a distinct memory is formed and stored in the brain. Recent studies conducted with cell ablation techniques suggest that defined populations of neurons carry a specific memory trace, or engram. However, these provide “loss of function” evidence. “The final test of any hypothesis concerning memory engrams must be a mimicry experiment in which apparent memory is manifested artificially without the usual requirement for sensory information…” (Martin and Morris, 2002). To this end, we have shown that in mice, the optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behavior in the context not used for conditioning. These data combined with those from various control experiments demonstrated that a sparse but specific ensemble of hippocampal neurons bear the engram of a specific memory, and its activation is sufficient for the recall of that memory.
While memories are usually good guides for behaviors, they can also be quite unreliable and have serious consequences in legal settings. However, the lack of relevant animal models has largely hindered our understanding of false memory formation. The development of the technology to identify and activate memory engram-bearing cells created a way to investigate neural mechanisms underlying false memories. Specifically, we hypothesized that a false memory could be generated by an association of an internally activated memory of a previous experience with a concurrently delivered external stimulus of high valence. We found such a false memory is indeed formed in mouse when the contextual engram formed previously is artificially activated subsequently by optogenetic stimulation while the footshock is delivered in a context that is distinct of the original context.
Modular organization of the grid map
Professor Edvard Moser, NTNU, Norway
The medial entorhinal cortex (MEC) is part of the brain’s circuit for dynamic representation of self-location. The metric of this representation is provided by grid cells, cells with spatial firing fields that tile environments in a periodic hexagonal pattern. Limited anatomical sampling has obscured whether the grid system operates as a unified system or a conglomerate of independent modules. Based on recordings from up to 186 grid cells in individual rats, we were able to show that grid cells cluster into a small number of layer-spanning anatomically-overlapping modules with distinct scale, orientation, asymmetry, and theta-frequency modulation. Although modules with small grid scales are located more dorsally than modules with larger scales, the modules exhibit considerable anatomical overlap, cutting across cell layers as well as widespread regions along both axes of the MEC sheet, suggesting that, within the same anatomical space, there are multiple cell groups with strong internal connectivity and weak cross-connectivity. The modules were able to respond independently to changes in the geometry of the environment. A significant scale relationship was revealed when increases in grid spacing were plotted across animals as a function of module number, with modules ranked according to their mean grid spacing. The scale ratio between successive module averages fluctuated around a constant value of 1.42, with a standard deviation of only 0.02, suggesting that grid scale follows a geometric progression rule. Similar modularity was not found in head direction cells, despite the presence of a dorsoventral gradient in directional tuning. The discrete topography of the grid-map, and the apparent autonomy of the modules, differ from the graded topography of maps for continuous variables in several sensory systems, raising the possibility that the modularity of the grid-map is a product of local self-organizing network dynamics. The lack of modules in head direction cells is consistent with the idea that grid modularity reflects the unique inhibitory network architecture of MEC layer II, where many grid cells are located, whereas the smoother organization of head direction cells may reflect the lack of such organization in layers III-VI, where most head direction cells are found.