TY - JOUR AB - The execution of cognitive functions requires coordinated circuit activity across different brain areas that involves the associated firing of neuronal assemblies. Here, we tested the circuit mechanism behind assembly interactions between the hippocampus and the medial prefrontal cortex (mPFC) of adult rats by recording neuronal populations during a rule-switching task. We identified functionally coupled CA1-mPFC cells that synchronized their activity beyond that expected from common spatial coding or oscillatory firing. When such cell pairs fired together, the mPFC cell strongly phase locked to CA1 theta oscillations and maintained consistent theta firing phases, independent of the theta timing of their CA1 counterpart. These functionally connected CA1-mPFC cells formed interconnected assemblies. While firing together with their CA1 assembly partners, mPFC cells fired along specific theta sequences. Our results suggest that upregulated theta oscillatory firing of mPFC cells can signal transient interactions with specific CA1 assemblies, thus enabling distributed computations. AU - Nardin, Michele AU - Käfer, Karola AU - Stella, Federico AU - Csicsvari, Jozsef L ID - 14314 IS - 9 JF - Cell Reports TI - Theta oscillations as a substrate for medial prefrontal-hippocampal assembly interactions VL - 42 ER - TY - JOUR AB - Although much is known about how single neurons in the hippocampus represent an animal's position, how circuit interactions contribute to spatial coding is less well understood. Using a novel statistical estimator and theoretical modeling, both developed in the framework of maximum entropy models, we reveal highly structured CA1 cell-cell interactions in male rats during open field exploration. The statistics of these interactions depend on whether the animal is in a familiar or novel environment. In both conditions the circuit interactions optimize the encoding of spatial information, but for regimes that differ in the informativeness of their spatial inputs. This structure facilitates linear decodability, making the information easy to read out by downstream circuits. Overall, our findings suggest that the efficient coding hypothesis is not only applicable to individual neuron properties in the sensory periphery, but also to neural interactions in the central brain. AU - Nardin, Michele AU - Csicsvari, Jozsef L AU - Tkačik, Gašper AU - Savin, Cristina ID - 14656 IS - 48 JF - The Journal of Neuroscience TI - The structure of hippocampal CA1 interactions optimizes spatial coding across experience VL - 43 ER - TY - THES AB - The ability to form and retrieve memories is central to survival. In mammals, the hippocampus is a brain region essential to the acquisition and consolidation of new memories. It is also involved in keeping track of one’s position in space and aids navigation. Although this space-memory has been a source of contradiction, evidence supports the view that the role of the hippocampus in navigation is memory, thanks to the formation of cognitive maps. First introduced by Tolman in 1948, cognitive maps are generally used to organize experiences in memory; however, the detailed mechanisms by which these maps are formed and stored are not yet agreed upon. Some influential theories describe this process as involving three fundamental steps: initial encoding by the hippocampus, interactions between the hippocampus and other cortical areas, and long-term extra-hippocampal consolidation. In this thesis, I will show how the investigation of cognitive maps of space helped to shed light on each of these three memory processes. The first study included in this thesis deals with the initial encoding of spatial memories in the hippocampus. Much is known about encoding at the level of single cells, but less about their co-activity or joint contribution to the encoding of novel spatial information. I will describe the structure of an interaction network that allows for efficient encoding of noisy spatial information during the first exploration of a novel environment. The second study describes the interactions between the hippocampus and the prefrontal cortex (PFC), two areas directly and indirectly connected. It is known that the PFC, in concert with the hippocampus, is involved in various processes, including memory storage and spatial navigation. Nonetheless, the detailed mechanisms by which PFC receives information from the hippocampus are not clear. I will show how a transient improvement in theta phase locking of PFC cells enables interactions of cell pairs across the two regions. The third study describes the learning of behaviorally-relevant spatial locations in the hippocampus and the medial entorhinal cortex. I will show how the accumulation of firing around goal locations, a correlate of learning, can shed light on the transition from short- to long-term spatial memories and the speed of consolidation in different brain areas. The studies included in this thesis represent the main scientific contributions of my Ph.D. They involve statistical analyses and models of neural responses of cells in different brain areas of rats executing spatial tasks. I will conclude the thesis by discussing the impact of the findings on principles of memory formation and retention, including the mechanisms, the speed, and the duration of these processes. AU - Nardin, Michele ID - 11932 SN - 2663-337X TI - On the encoding, transfer, and consolidation of spatial memories ER - TY - GEN AB - Hippocampal and neocortical neural activity is modulated by the position of the individual in space. While hippocampal neurons provide the basis for a spatial map, prefrontal cortical neurons generalize over environmental features. Whether these generalized representations result from a bidirectional interaction with, or are mainly derived from hippocampal spatial representations is not known. By examining simultaneously recorded hippocampal and medial prefrontal neurons, we observed that prefrontal spatial representations show a delayed coherence with hippocampal ones. We also identified subpopulations of cells in the hippocampus and medial prefrontal cortex that formed functional cross-area couplings; these resembled the optimal connections predicted by a probabilistic model of spatial information transfer and generalization. Moreover, cross-area couplings were strongest and had the shortest delay preceding spatial decision-making. Our results suggest that generalized spatial coding in the medial prefrontal cortex is inherited from spatial representations in the hippocampus, and that the routing of information can change dynamically with behavioral demands. AU - Nardin, Michele AU - Käfer, Karola AU - Csicsvari, Jozsef L ID - 10080 T2 - bioRxiv TI - The generalized spatial representation in the prefrontal cortex is inherited from the hippocampus ER - TY - JOUR AB - The brain efficiently performs nonlinear computations through its intricate networks of spiking neurons, but how this is done remains elusive. While nonlinear computations can be implemented successfully in spiking neural networks, this requires supervised training and the resulting connectivity can be hard to interpret. In contrast, the required connectivity for any computation in the form of a linear dynamical system can be directly derived and understood with the spike coding network (SCN) framework. These networks also have biologically realistic activity patterns and are highly robust to cell death. Here we extend the SCN framework to directly implement any polynomial dynamical system, without the need for training. This results in networks requiring a mix of synapse types (fast, slow, and multiplicative), which we term multiplicative spike coding networks (mSCNs). Using mSCNs, we demonstrate how to directly derive the required connectivity for several nonlinear dynamical systems. We also show how to carry out higher-order polynomials with coupled networks that use only pair-wise multiplicative synapses, and provide expected numbers of connections for each synapse type. Overall, our work demonstrates a novel method for implementing nonlinear computations in spiking neural networks, while keeping the attractive features of standard SCNs (robustness, realistic activity patterns, and interpretable connectivity). Finally, we discuss the biological plausibility of our approach, and how the high accuracy and robustness of the approach may be of interest for neuromorphic computing. AU - Nardin, Michele AU - Phillips, James W. AU - Podlaski, William F. AU - Keemink, Sander W. ID - 10635 JF - Peer Community Journal TI - Nonlinear computations in spiking neural networks through multiplicative synapses VL - 1 ER - TY - GEN AB - Although much is known about how single neurons in the hippocampus represent an animal’s position, how cell-cell interactions contribute to spatial coding remains poorly understood. Using a novel statistical estimator and theoretical modeling, both developed in the framework of maximum entropy models, we reveal highly structured cell-to-cell interactions whose statistics depend on familiar vs. novel environment. In both conditions the circuit interactions optimize the encoding of spatial information, but for regimes that differ in the signal-to-noise ratio of their spatial inputs. Moreover, the topology of the interactions facilitates linear decodability, making the information easy to read out by downstream circuits. These findings suggest that the efficient coding hypothesis is not applicable only to individual neuron properties in the sensory periphery, but also to neural interactions in the central brain. AU - Nardin, Michele AU - Csicsvari, Jozsef L AU - Tkačik, Gašper AU - Savin, Cristina ID - 10077 T2 - bioRxiv TI - The structure of hippocampal CA1 interactions optimizes spatial coding across experience ER - TY - JOUR AB - Temporally organized reactivation of experiences during awake immobility periods is thought to underlie cognitive processes like planning and evaluation. While replay of trajectories is well established for the hippocampus, it is unclear whether the medial prefrontal cortex (mPFC) can reactivate sequential behavioral experiences in the awake state to support task execution. We simultaneously recorded from hippocampal and mPFC principal neurons in rats performing a mPFC-dependent rule-switching task on a plus maze. We found that mPFC neuronal activity encoded relative positions between the start and goal. During awake immobility periods, the mPFC replayed temporally organized sequences of these generalized positions, resembling entire spatial trajectories. The occurrence of mPFC trajectory replay positively correlated with rule-switching performance. However, hippocampal and mPFC trajectory replay occurred independently, indicating different functions. These results demonstrate that the mPFC can replay ordered activity patterns representing generalized locations and suggest that mPFC replay might have a role in flexible behavior. AU - Käfer, Karola AU - Nardin, Michele AU - Blahna, Karel AU - Csicsvari, Jozsef L ID - 7472 IS - 1 JF - Neuron SN - 0896-6273 TI - Replay of behavioral sequences in the medial prefrontal cortex during rule switching VL - 106 ER - TY - DATA AB - Open the files in Jupyter Notebook (reccomended https://www.anaconda.com/distribution/#download-section with Python 3.7). AU - Nardin, Michele ID - 6062 TI - Supplementary Code and Data for the paper "The Entorhinal Cognitive Map is Attracted to Goals" ER - TY - JOUR AB - Grid cells with their rigid hexagonal firing fields are thought to provide an invariant metric to the hippocampal cognitive map, yet environmental geometrical features have recently been shown to distort the grid structure. Given that the hippocampal role goes beyond space, we tested the influence of nonspatial information on the grid organization. We trained rats to daily learn three new reward locations on a cheeseboard maze while recording from the medial entorhinal cortex and the hippocampal CA1 region. Many grid fields moved toward goal location, leading to long-lasting deformations of the entorhinal map. Therefore, distortions in the grid structure contribute to goal representation during both learning and recall, which demonstrates that grid cells participate in mnemonic coding and do not merely provide a simple metric of space. AU - Boccara, Charlotte N. AU - Nardin, Michele AU - Stella, Federico AU - O'Neill, Joseph AU - Csicsvari, Jozsef L ID - 6194 IS - 6434 JF - Science SN - 0036-8075 TI - The entorhinal cognitive map is attracted to goals VL - 363 ER -