Temporal patterns of spiking activity in the hippocampal formation

The process of faithfully retrieving episodes from our memory requires a neural mechanism capable of initially forming ordered and reliable behavioral sequences. These behavioral sequences take place on a timescale of seconds or more, whereas the timescale of neural plasticity and learning is in the order of tens of milliseconds. To shed light on this dilemma, we turn to studies of hippocampal place cells in rodents, i.e., cells that selectively increase their firing rates in locations of the environment known as the place fields. Within a field, the firing phases of a place cell precess monotonically relative to the ongoing theta rhythm. This phenomenon, termed "phase precession", leads to a temporally compressed representation of the behavioral sequences experienced by the rodent, and the compressed timescale matches the requirements of neural plasticity. In this thesis, I study the mechanisms and functions of phase precession by proposing a framework that relies on the concept of inheritance: the simple idea that patterns of neural activity can be propagated from one region to another. Indeed, phase precession has been observed in several regions of the hippocampus and entorhinal cortex, and an important open question is whether phase precession emerges independently in each region, or conversely, whether phase precession can be "inherited" from an upstream neuronal population. The inheritance framework consists of analyzing the spiking activity of cells in feed-forward topologies, where a set of input cells project and convey excitatory input to a target cell. First, I study the possibility that CA1 cells in the hippocampus inherit their phase precession from CA3 cells. I find that this simple hypothesis can explain the sub and suprathreshold dynamics of CA1 cells (Harvey et al., 2009; Mizuseki et al., 2012). Furthermore, I elucidate roles for excitation and inhibition in determining a CA1 place cell’s response. In particular, I interpret the results of a recent experiment where interneurons from the CA1 region in the hippocampus were silenced using optogenetics (Royer et al., 2012). An issue closely related to phase-precession inheritance, is that of place-field inheritance. Thus, I study in a computational model how place-selectivity can naturally arise in CA1 cells if CA3 inputs have distributed spatial tuning and CA3-CA1 synapses are endowed with spike-timing-dependent plasticity. I examine the conditions that allow for place-field formation in CA1 cells even if the initial distribution of CA3-CA1 synaptic weights is random. The model predicts that theta modulation and phase precession of the input CA3 cells favor the inheritance process, i.e., the time for structure formation in a CA1 cell is reduced compared to the case of no input modulation. Next, I develop the inheritance framework further and show how the simple feedforward topologies in the hippocampal formation assist in propagating phase precession to different regions of the hippocampus and adjacent structures. I explain how the placeselective responses of a given cell are influenced by the spatial distribution of place-field centers at the input. The inheritance framework can account for, for example, the little incidence of phase precession in interneurons (Skaggs et al., 1996), the characteristic shape of phase precession for ramp cells in the ventral striatum (van der Meer and Redish, 2011), and phase-precessing place cells that receive input from phase-precessing grid cells (Hafting et al., 2008). These results suggest that the presence of phase precession in different stages of the hippocampal circuit and other regions of the brain is indicative of a common source, a fact that can help us better understand the temporal spiking patterns in the brain. Finally, I critically review the current evidence for a behavioral role for phase precession and suggest a roadmap for future research in this field.