A General Hippocampal Computational Model Combining Episodic and Spatial Memory in a Spiking Model

Institute for Adaptive and Neural ComputationThe hippocampus, in humans and rats, plays crucial roles in spatial tasks and nonspatial tasks involving episodic-type memory. This thesis presents a novel computational model of the hippocampus (CA1, CA3 and dentate gyrus) which creates a framework where spatial memory and episodic memory are explained together. This general model follows the approach where the memory function of the rodent hippocampus is seen as a “memory space” instead of a “spatial memory”. The innovations of this novel model are centred around the fact that it follows detailed hippocampal architecture constraints and uses spiking networks to represent all hippocampal subfields. This hippocampal model does not require stable attractor states to produce a robust memory system capable of pattern separation and pattern completion. In this hippocampal theory, information is represented and processed in the form of activity patterns. That is, instead of assuming firing-rate coding, this model assumes that information is coded in the activation of specific constellations of neurons. This coding mechanism, associated with the use of spiking neurons, raises many problems on how information is transferred, processed and stored in the different hippocampal subfields. This thesis explores which mechanisms are available in the hippocampus to achieve such control, and produces a detailed model which is biologically realistic and capable of explaining how several computational components can work together to produce the emergent functional properties of the hippocampus. In this hippocampal theory, precise explanations are given to why mossy fibres are important for storage but not recall, what is the functional role of the mossy cells (excitatory interneurons) in the dentate gyrus, why firing fields can be asymmetric with the firing peak closer to the end of the field, which features are used to produce “place fields”, among others. An important property of this hippocampal model is that the memory system provided by the CA3 is a palimpsest memory: after saturation, the number of patterns that can be recalled is independent of the number of patterns engraved in the recurrent network. In parallel with the development of the hippocampal computational model, a simulation environment was created. This simulation environment was tailored for the needs and assumptions of the hippocampal model and represents an important component of this thesis

Distributed Encoding of Spatial and Object Categories in Primate Hippocampal Microcircuits

The primate hippocampus plays critical roles in the encoding, representation, categorization and retrieval of cognitive information. Such cognitive abilities may use the transformational input-output properties of hippocampal laminar microcircuitry to generate spatial representations and to categorize features of objects, images, and their numeric characteristics. Four nonhuman primates were trained in a delayed-match-to-sample (DMS) task while multi-neuron activity was simultaneously recorded from the CA1 and CA3 hippocampal cell fields. The results show differential encoding of spatial location and categorization of images presented as relevant stimuli in the task. Individual hippocampal cells encoded visual stimuli only on specific types of trials in which retention of either, the Sample image, or the spatial position of the Sample image indicated at the beginning of the trial, was required. Consistent with such encoding, it was shown that patterned microstimulation applied during Sample image presentation facilitated selection of either Sample image spatial locations or types of images, during the Match phase of the task. These findings support the existence of specific codes for spatial and numeric object representations in primate hippocampus which can be applied on differentially signaled trials. Moreover, the transformational properties of hippocampal microcircuitry, together with the patterned microstimulation are supporting the practical importance of this approach for cognitive enhancement and rehabilitation, needed for memory neuroprosthetics

The mechanisms for pattern completion and pattern separation in the hippocampus

The mechanisms for pattern completion and pattern separation are described in the context of a theory of hippocampal function in which the hippocampal CA3 system operates as a single attractor or autoassociation network to enable rapid, one-trial, associations between any spatial location (place in rodents, or spatial view in primates) and an object or reward, and to provide for completion of the whole memory during recall from any part. The factors important in the pattern completion in CA3 together with a large number of independent memories stored in CA3 include a sparse distributed representation which is enhanced by the graded firing rates of CA3 neurons, representations that are independent due to the randomizing effect of the mossy fibers, heterosynaptic long-term depression as well as long-term potentiation in the recurrent collateral synapses, and diluted connectivity to minimize the number of multiple synapses between any pair of CA3 neurons which otherwise distort the basins of attraction. Recall of information from CA3 is implemented by the entorhinal cortex perforant path synapses to CA3 cells, which in acting as a pattern associator allow some pattern generalization. Pattern separation is performed in the dentate granule cells using competitive learning to convert grid-like entorhinal cortex firing to place-like fields. Pattern separation in CA3, which is important for completion of any one of the stored patterns from a fragment, is provided for by the randomizing effect of the mossy fiber synapses to which neurogenesis may contribute, by the large number of dentate granule cells each with a sparse representation, and by the sparse independent representations in CA3. Recall to the neocortex is achieved by a reverse hierarchical series of pattern association networks implemented by the hippocampo-cortical backprojections, each one of which performs some pattern generalization, to retrieve a complete pattern of cortical firing in higher-order cortical areas

A Mismatch-Based Model for Memory Reconsolidation and Extinction in Attractor Networks

The processes of memory reconsolidation and extinction have received increasing attention in recent experimental research, as their potential clinical applications begin to be uncovered. A number of studies suggest that amnestic drugs injected after reexposure to a learning context can disrupt either of the two processes, depending on the behavioral protocol employed. Hypothesizing that reconsolidation represents updating of a memory trace in the hippocampus, while extinction represents formation of a new trace, we have built a neural network model in which either simple retrieval, reconsolidation or extinction of a stored attractor can occur upon contextual reexposure, depending on the similarity between the representations of the original learning and reexposure sessions. This is achieved by assuming that independent mechanisms mediate Hebbian-like synaptic strengthening and mismatch-driven labilization of synaptic changes, with protein synthesis inhibition preferentially affecting the former. Our framework provides a unified mechanistic explanation for experimental data showing (a) the effect of reexposure duration on the occurrence of reconsolidation or extinction and (b) the requirement of memory updating during reexposure to drive reconsolidation

Neural Encoding of Local vs. Global Space: From Structure to Function

The retrosplenial cortex may be important for navigating visually similar compartmentalised spaces by conjunctively encoding both local and global environments. Previously, a novel directional signal that encodes local spaces was found in the dysgranular retrosplenial cortex (dRSC) while global head direction encoding was found in both dRSC and granular retrosplenial cortex (gRSC; Jacob et al., 2017). This thesis addresses two questions arising from this finding: (i) how does the local directional signal arise? and (ii) do the downstream place cells (cells that display spatially constrained firing) display local or global encoding? The first question was explored by retrogradely labelling the neuronal inputs into the two retrosplenial regions under the hypothesis that the differences in directional encoding are due to differences in their inputs. Particularly, gRSC was found to receive more inputs from anterodorsal thalamus, which was previously shown to display global encoding (Jacob et al., 2017). In addition, gRSC, but not dRSC, received inputs from dorsal subiculum which is the main output structure of hippocampus. It is however unclear if place cell in hippocampus displayed local or global place encoding. The second question thus arises: Do place cells display local or global place encoding? As hippocampus is strongly coupled with gRSC, place cells were predicted to show a global representation similar to that in gRSC. Extracellular recording of place cells in an environment with two differentially scented, visually rotated compartments showed that no place cells that are sensitive to the local visual scene were found. Thus, place cells displayed global encoding. Together, these findings indicate that global encoding in gRSC may be a consequence of its stronger coupling with vestibular-directional nuclei and the hippocampal system, both of which displayed global encoding. In contrast, the local encoding observed in dRSC may reflect its structural disconnect from the global spatial network

Doctor of Philosophy

dissertationDorsoventral lesion studies of the hippocampus (HPP) have suggested that the dorsal axis is important for spatial processing and the ventral axis is involved in olfactory learning and memory as well as anxiety. Accrued reports have indicated that subregions along the dorsal axis play specialized roles in spatial information processes and there is some evidence to indicate that the ventral CA3 and ventral CA1 subregions are involved in cued retrieval in fear conditioning and also carry out olfactory learning and memory processes similar to dorsal axis counterparts. The current study investigated the less-understood role of the ventral DG in olfaction and anxiety. A series of odor stimuli were used that provide a range of differentiation on only one level in a matching-to-sample paradigm to investigate ventral DG involvement in working memory for similar and less similar odors, in which there was a memory-based pattern separation effect. A novelty detection paradigm was used to investigate ventral DG involvement in recognition of familiar and new social odors. Finally, an elevated-plus maze and open field maze were selected in order to investigate the role of the ventral DG in the ability to modify behavior in potentially dangerous environments. The current study has provided evidence to suggest that the ventral DG plays an important role in olfactory learning and memory processes as well as anxiety-based behaviors during exploration in anxiety-provoking environments

Neural correlates of navigation in large-scale space

Navigation and self-localisation are fundamental to spatial cognition. The cognitive map supporting these abilities is implemented in the hippocampal formation. Place cells in the hippocampus fire when the animal is at a specific location – a place field. They are thought to be involved in navigation and self-localisation but usually studied in constrained environments, limiting observable states. In this thesis, I present two experiments studying place cells in large open field environments, a novel auditory cue-triggered navigational task, and a technical solution for conducting large scale automated experiments. Place cells are frequently reactivated during immobility, rapidly replaying trajectories through environments. These replay events are thought to be involved in navigational planning. Using a novel automated cue-triggered navigational task in a large open field environment, I show that replay is not associated with navigation to the goal. Instead, it occurs reliably at the end of successful trials, when an associated reward is received, but not during consumption of scattered pellets. The trajectories in these events are predictive of the animal’s movement after, but not before, the reward. The number of place fields per cell, their size and other properties have not been fully characterised. Using multiple large open field environments of different size, I show that place field size, shape and density changes systematically with distance from walls. However, through a homeostatic mechanism, the mean firing rate and proportion of co-active units in the population remains constant throughout environments, as does the accuracy of their spatial representation. Multiple place field properties are conserved by cells across environments, including the number of fields, which is quantified relative to environment size using a gamma-Poisson model. Place cell population models suggest two sub-populations, with uniform and boundary dependent field distributions. These results provide a comprehensive account of place cell population statistics in different size environments