Laleh K. Quinn

Temporally selective contextual encoding in the dentate gyrus of the hippocampus

A recent model of the hippocampus predicts that the unique properties of the dentate gyrus allow for temporal separation of events. This temporal separation is accomplished in part through the continual generation of new neurons, which, due to a transient window of hyperexcitability, could allow for preferential encoding of information present during their development. Here we obtain in vivo electrophysiological recordings and identify a cell population exhibiting activity that is selective to single contexts when rats experience a long temporal separation between context exposures during training. This selectivity is attenuated as the temporal separation between context exposures is shortened and is further attenuated when neurogenesis is reduced. Our data reveal the existence of a temporal orthogonalizing neuronal code within the dentate gyrus, a hallmark feature of episodic memory.

A Hypothesis for Temporal Coding of Young and Mature Granule Cells.

While it has been hypothesized that adult neurogenesis (NG) plays a role in the encoding of temporal information at long time-scales, the temporal relationship of immature cells to the highly rhythmic network activity of the hippocampus has been largely unexplored. Here, we present a theory for how the activity of immature adult-born granule cells relates to hippocampal oscillations. Our hypothesis is that theta rhythmic (5–10 Hz) excitatory and inhibitory inputs into the hippocampus could differentially affect young and mature granule cells due to differences in intrinsic physiology and synaptic inhibition between the two cell populations. Consequently, immature cell activity may occur at broader ranges of theta phase than the activity of their mature counterparts. We describe how this differential influence on young and mature granule cells could separate the activity of differently aged neurons in a temporal coding regime. Notably, this process could have considerable implications on how the downstream CA3 region interprets the information conveyed by young and mature granule cells. To begin to investigate the phasic behavior of granule cells, we analyzed in vivo recordings of the rat dentate gyrus (DG), observing that the temporal behavior of granule cells with respect to the theta rhythm is different between rats with normal and impaired levels of NG. Specifically, in control animals, granule cells exhibit both strong and weak coupling to the phase of the theta rhythm. In contrast, the distribution of phase relationships in NG-impaired rats is shifted such that they are significantly stronger. These preliminary data support our hypothesis that immature neurons could distinctly affect the temporal dynamics of hippocampal encoding.

Learning‐dependent dynamics of beta‐frequency oscillations in the basal forebrain of rats

Cholinergic, GABAergic and glutamatergic projection neurons of the basal forebrain (BF) innervate widespread regions of the neocortex and are thought to modulate learning and attentional processes. Although it is known that neuronal cell types in the BF exhibit oscillatory firing patterns, whether the BF as a whole shows oscillatory field potential activity, and whether such neuronal patterns relate to components of cognitive tasks, has yet to be determined. To this end, local field potentials (LFPs) were recorded from the BF of rats performing an associative learning task wherein neutral objects were paired with differently valued reinforcers (pellets). Over time, rats developed preferences for the different objects based on pellet‐value, indicating that the pairings had been well learned. LFPs from all rats revealed robust, short‐lived bursts of beta‐frequency oscillations (∼25 Hz) around the time of object encounter. Beta‐frequency LFP events were found to be learning‐dependent, with beta‐frequency peak amplitudes significantly greater on the first day of the task when object–reinforcement pairings were novel than on the last day when pairings were well learned. The findings indicate that oscillatory bursting field potential activity occurs in the BF in freely behaving animals. Furthermore, the temporal distribution of these bursts suggests that they are probably relevant to associative learning.

Cell Assemblies of the Basal Forebrain

The basal forebrain comprises several heterogeneous neuronal subgroupings having modular projection patterns to discrete sets of cortical subregions. Each cortical region forms recurrent projections, via prefrontal cortex, that reach the specific basal forebrain subgroups from which they receive afferents. This architecture enables the basal forebrain to selectively modulate cortical responsiveness according to current processing demands. Theoretically, optimal functioning of this distributed network would be enhanced by temporal coordination among coactive basal forebrain neurons, or the emergence of “cell assemblies.” The present work demonstrates assembly formation in rat basal forebrain neuronal populations during a selective attention task. Neuron pairs exhibited coactivation patterns organized within beta-frequency time windows (55 ms), regardless of their membership within distinct bursting versus nonbursting basal forebrain subpopulations. Thus, the results reveal a specific temporal framework for integration of information within basal forebrain networks and for the modulation of cortical responsiveness.

Theta and beta oscillatory dynamics in the dentate gyrus reveal a shift in network processing state during cue encounters

The hippocampus is an important structure for learning and memory processes, and has strong rhythmic activity. Although a large amount of research has been dedicated toward understanding the rhythmic activity in the hippocampus during exploratory behaviors, specifically in the theta (5–10 Hz) frequency range, few studies have examined the temporal interplay of theta and other frequencies during the presentation of meaningful cues. We obtained in vivo electrophysiological recordings of local field potentials (LFP) in the dentate gyrus (DG) of the hippocampus as rats performed three different associative learning tasks. In each task, cue presentations elicited pronounced decrements in theta amplitude in conjunction with increases in beta (15–30 Hz) amplitude. These changes were often transient but were sustained from the onset of cue encounters until the occurrence of a reward outcome. This oscillatory profile shifted in time to precede cue encounters over the course of the session, and was not present during similar behaviors in the absence of task relevant stimuli. The observed decreases in theta amplitude and increases in beta amplitude in the DG may thus reflect a shift in processing state that occurs when encountering meaningful cues.

Rat meets iRat

Biorobotics has the potential to provide an integrated understanding from neural systems to behavior that is neither ethical nor technically feasible with living systems. Robots that can interact with animals in their natural environment open new possibilities for empirical studies in neuroscience. However, designing a robot that can interact with a rodent requires considerations that span a range of disciplines. For the rats safety, the body form and movements of the robot need to take into consideration the safety of the animal, an appropriate size for the rodent arenas, and behaviors for interaction. For the robots safety, its form must be robust in the face of typically inquisitive and potentially aggressive behaviors by the rodent, which can include chewing on exposed parts, including electronics, and deliberate or accidental fouling. We designed a rat-sized robot, the iRat (intelligent rat animat technology) for studies in neuroscience. The iRat is about the same size as a rat and has the ability to navigate autonomously around small environments. In this study we report the first interactions between the iRat and real rodents in a free exploration task. Studies with five rats show that the rats and iRat interact safely for both parties.

Transformation of Independent Oscillatory Inputs into Temporally Precise Rate Codes

Complex behaviors demand temporal coordination among functionally distinct brain regions. The basal forebrain’s afferent and efferent structure suggests a capacity for mediating such coordination. During performance of a selective attention task, synaptic activity in this region was dominated by four amplitude-independent oscillations temporally organized by the phase of the slowest, a theta rhythm. Further, oscillatory amplitudes were precisely organized by task epoch and a robust input/output transform, from synchronous synaptic activity to spiking rates of basal forebrain neurons, was identified. For many neurons, spiking was temporally organized as phase precessing sequences against theta band field potential oscillations. Remarkably, theta phase precession advanced in parallel to task progression, rather than absolute spatial location or time. Together, the findings reveal a process by which associative brain regions can integrate independent oscillatory inputs and transform them into sequence-specific, rate-coded outputs that are adaptive to the pace with which organisms interact with their environment.

Multiplexed oscillations and phase rate coding in the basal forebrain

Basal forebrain transforms multiplexed oscillatory inputs into a phase rate–coded output of task phase during complex behavior. Complex behaviors demand temporal coordination among functionally distinct brain regions. The basal forebrain’s afferent and efferent structure suggests a capacity for mediating this coordination at a large scale. During performance of a spatial orientation task, synaptic activity in this region was dominated by four amplitude-independent oscillations temporally organized by the phase of the slowest, a theta-frequency rhythm. Oscillation amplitudes were also organized by task epoch and positively correlated to the task-related modulation of individual neuron firing rates. For many neurons, spiking was temporally organized through phase precession against theta band field potential oscillations. Theta phase precession advanced in parallel to task progression, rather than absolute spatial location or time. Together, the findings reveal a process by which associative brain regions can integrate independent oscillatory inputs and transform them into sequence-specific, rate-coded outputs that are adaptive to the pace with which organisms interact with their environment.

Space, Time, and the Hippocampus

Kesner’s attribute model of memory endows the hippocampus with the ability to code both time and space. These two parameters are intertwined in their very essence and lend structure to the ongoing autobiographical record of an organism. Kesner’s addition of time and temporal processing to the notion that the hippocampus supports a spatial cognitive map, fused hippocampal theory into a coherent framework for human and non-human animals. The mechanism by which the hippocampus and its associated circuitry supports memory for time is a fertile area of research that was seeded by Kesner and his contemporaries. The inherent physiological properties of the hippocampus support Kesner’s original hypothesis, emphasizing that temporal and spatial inputs converge in the hippocampus. The temporal scale of this convergence is evident from patterns of neuronal firing to enduring memories.