Deliberative Behaviors and Prefrontal-Hippocampal Coupling are Disrupted in a Rat Model of Fetal Alcohol Spectrum Disorders.

Fetal alcohol spectrum disorders (FASDs) are characterized by a range of physical, cognitive, and behavioral impairments. Determining how temporally specific alcohol exposure (AE) affects neural circuits is crucial to understanding the FASD phenotype. Third trimester AE can be modeled in rats by administering alcohol during the first two postnatal weeks, which damages the medial prefrontal cortex (mPFC), thalamic nucleus reuniens, and hippocampus (HPC), structures whose functional interactions are required for working memory and executive function.

Pausing and reorienting behaviors enhance the performance of a spatial working memory task.

During spatial working memory tasks, animals need to retain information about a previous trial in order to successfully select their next trajectory. Specifically, the delayed non-match to position task requires rats to follow a cued sample trajectory, then select the opposite route after a delay period. When faced with this choice, rats will occasionally exhibit complex behaviors, such as pausing and sweeping their head back and forth.

The ventral midline thalamus coordinates prefrontal-hippocampal neural synchrony during vicarious trial and error.

When faced with difficult choices, the possible outcomes are considered through a process known as deliberation. In rats, deliberation is thought to be reflected by pause-and-reorienting behaviors, better known as vicarious trial and errors (VTEs). While VTEs are thought to require medial prefrontal cortex (mPFC) and dorsal hippocampal (dHPC) interactions, no empirical evidence has yet demonstrated such a dual requirement.

Optogenetic suppression of the medial septum impairs working memory maintenance.

Spatial working memory (SWM) is the ability to encode, maintain, and retrieve spatial information over a temporal gap, and relies on a network of structures including the medial septum (MS), which provides critical input to the hippocampus. Although the role of the MS in SWM is well-established, up until recently, we have been unable to use temporally precise circuit manipulation techniques to examine the specific role of the MS in SWM, particularly to distinguish between encoding, maintenance, and retrieval. Here, we test the hypothesis that the MS supports the maintenance of spatial information over a temporal gap using precisely timed optogenetic suppression delivered during specific portions of three different tasks, two of which rely on SWM and one that does not.

The nucleus reuniens orchestrates prefrontal-hippocampal synchrony during spatial working memory.

Spatial working memory, the ability to temporarily maintain an internal representation of spatial information for use in guiding upcoming decisions, has been shown to be dependent upon a network of brain structures that includes the hippocampus, a region known to be critical for spatial navigation and episodic memory, and the prefrontal cortex (PFC), a region known to be critical for executive function and goal directed behavior. Oscillatory synchronization between the hippocampus and the prefrontal cortex (PFC) is known to increase in situations of high working memory demand. Most of our knowledge about the anatomical connectivity between the PFC and hippocampus comes from the rodent literature.

Representations of On-Going Behavior and Future Actions During a Spatial Working Memory Task by a High Firing-Rate Population of Medial Prefrontal Cortex Neurons.

Spatial working memory (SWM) requires the encoding, maintenance, and retrieval of spatially relevant information to guide decision-making. The medial prefrontal cortex (mPFC) has long been implicated in the ability of rodents to perform SWM tasks. While past studies have demonstrated that mPFC ensembles reflect past and future experiences, most findings are derived from tasks that have an experimental overlap between the encoding and retrieval of trajectory specific information.

The nucleus reuniens of the thalamus sits at the nexus of a hippocampus and medial prefrontal cortex circuit enabling memory and behavior.

The nucleus reuniens of the thalamus (RE) is a key component of an extensive network of hippocampal and cortical structures and is a fundamental substrate for cognition. A common misconception is that RE is a simple relay structure. Instead, a better conceptualization is that RE is a critical component of a canonical higher-order cortico-thalamo-cortical circuit that supports communication between the medial prefrontal cortex (mPFC) and the hippocampus (HC).

Optogenetic suppression of the nucleus reuniens selectively impairs encoding during spatial working memory.

The nucleus reuniens (Re) of the ventral midline thalamus is known to be a critical anatomical link between the hippocampus (HPC) and the medial prefrontal cortex (mPFC). Consistent with this anatomical connectivity, the Re has been shown to be crucial for HPC-mPFC oscillatory synchrony. Moreover, Re inhibition consistently results in spatial working memory (SWM) deficits.

Ventral Midline Thalamus Is Critical for Hippocampal-Prefrontal Synchrony and Spatial Working Memory.

Unlabelled: Maintaining behaviorally relevant information in spatial working memory (SWM) requires functional synchrony between the dorsal hippocampus and medial prefrontal cortex (mPFC). However, the mechanism that regulates synchrony between these structures remains unknown. Here, we used a unique dual-task approach to compare hippocampal-prefrontal synchrony while rats switched between an SWM-dependent task and an SWM-independent task within a single behavioral session.

Inactivation of the nucleus reuniens/rhomboid causes a delay-dependent impairment of spatial working memory.

Inactivation of the rodent medial prefrontal cortex (mPFC) and hippocampus or disconnection of the hippocampus from the mPFC produces deficits in spatial working memory tasks. Previous studies have shown that delay length determines the extent to which mPFC and hippocampus functionally interact, with both structures being necessary for tasks with longer delays and either structure being sufficient for tasks with shorter delays. In addition, inactivation of the nucleus reuniens (Re)/rhomboid nucleus (Rh) of the thalamus, which has bidirectional connections with the mPFC and hippocampus, also produces deficits in these tasks.

Comparing Color and Leader Line Highlighting Strategies in Coordinated View Geovisualizations.

In most coordinated view geovisualization tools, a transient visual effect is used to highlight observations across views when brushed with a mouse or other input device. Most current geovisualization and information visualization systems use colored outlines or fills to highlight observations, but there remain a wide range of alternative visual strategies that can also be implemented and compared to color highlighting to evaluate user performance. This paper describes the results of an experiment designed to compare user performance with two highlighting methods; color and leader lines.

Integrating paid work and chronic illness in daily life: A space-time approach to understanding the challenges.

The upward trend of chronic illness in working age populations calls for better understanding of the difficulties chronically ill people face with workforce participation. Existing research focuses primarily on physical limitations and employer attitudes about chronic illness. Here we use a space-time approach to illuminate the importance of negotiating logistical challenges and embodied rhythms when balancing work and chronic illness.

Role of the thalamic nucleus reuniens in mediating interactions between the hippocampus and medial prefrontal cortex during spatial working memory.

Despite decades of research, the neural mechanisms of spatial working memory remain poorly understood. Although the dorsal hippocampus is known to be critical for memory-guided behavior, experimental evidence suggests that spatial working memory depends not only on the hippocampus itself, but also on the circuit comprised of the hippocampus and the medial prefrontal cortex (mPFC). Disruption of hippocampal-mPFC interactions may result in failed transfer of spatial and contextual information processed by the hippocampus to the circuitry in mPFC responsible for decision making and goal-directed behavior.

Transient inactivation of the medial prefrontal cortex impairs performance on a working memory-dependent conditional discrimination task.

The rodent medial prefrontal cortex (mPFC) has been implicated in working memory function; lesions and inactivation of this region have been shown to result in impairments in spatial working memory (WM) tasks. Our laboratory has developed a tactile-visual conditional discrimination (CD) task, which uses floor insert cues to signal the correct goal-arm choice in a T maze. This task can be manipulated by altering the floor insert cues to be present throughout the trial (CDSTANDARD) or to be present only at the beginning of the trial (CDWM), thus making the task either WM-independent or WM-dependent, respectively.

In vivo polymerization of poly(3,4-ethylenedioxythiophene) in the living rat hippocampus does not cause a significant loss of performance in a delayed alternation task.

After extended implantation times, traditional intracortical neural probes exhibit a foreign-body reaction characterized by a reactive glial sheath that has been associated with increased system impedance and signal deterioration. Previously, we have proposed that the local in vivo polymerization of an electronically and ionically conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), might help to rebuild charge transport pathways across the glial scar between the device and surrounding parenchyma (Richardson-Burns et al 2007 J. Neural Eng.

Transient inactivation of the thalamic nucleus reuniens and rhomboid nucleus produces deficits of a working-memory dependent tactile-visual conditional discrimination task.

Working memory depends on communication between the hippocampus and the prefrontal cortex (PFC); however, the neural circuitry that mediates interactions between these brain areas has not been well characterized. Two candidate structures are the thalamic reuniens (RE) and rhomboid (Rh) nuclei, which are reciprocally connected with both the hippocampus and PFC. These known anatomical connections suggest that RE/Rh may be involved in mediating hippocampal-prefrontal communication, and therefore may be critical for working memory processing.

Hippocampal signatures of episodic memory: evidence from single-unit recording studies.

What hippocampal neural firing patterns signal memory and, more importantly, how is this memory code used by associated structures to translate a memory into a decision or action? Candidate hippocampal activity patterns will be discussed including (1) trajectory-specific firing of place cells with place fields on an overlapping segment of two (or more) distinct trajectories (2) prospective firing of hippocampal neurons that signal an upcoming event or action, and (3) place cell remapping to changes in environment and task. To date, there has not been compelling evidence for any of these activity patterns being the neural substrate of episodic memory. New findings suggest that learning and memory processes are emergent properties of interregional interactions and not localized within any one discrete brain region.

Dissociable roles of the dorsal striatum and dorsal hippocampus in conditional discrimination and spatial alternation T-maze tasks.

The roles of the dorsal hippocampus (DH) and dorsal striatum (DS) in the learning and retention of conditional discrimination (CD) rules is a subject of debate. Although previous studies have examined the relationship between the DH and DS and the performance of CD tasks in operant chambers, the relative contributions of these two brain regions to the retention of CD rules requiring an association between a cue and a spatial location have not been characterized. We designed an experiment to assess the roles of the DH and DS in the retention of a visuospatial CD task by transiently inactivating either structure with muscimol in separate groups of rats and measuring performance on a previously learned CD task.

Dynamic coding of dorsal hippocampal neurons between tasks that differ in structure and memory demand.

Hippocampal place fields show remapping between environments that contain sufficiently different contextual features, a phenomenon that may reflect a mechanism for episodic memory formation. Previous studies have shown that place fields remap to changes in the configuration of visual landmarks in an environment. Other experiments have demonstrated that remapping can occur with experience, even when the visual features of an environment remain stable.

The role of the medial prefrontal cortex in the acquisition, retention, and reversal of a tactile visuospatial conditional discrimination task.

The medial prefrontal cortex (mPFC) is responsible for executive functions such as abstract rule coding, strategy switching, and behavioral flexibility; however, there is some debate regarding the extent to which mPFC is involved in reversal learning, especially in complex multisensory tasks such as conditional discrimination. Therefore, we investigated the effects of mPFC inactivation on the acquisition, retention, and reversal of a visuospatial conditional discrimination (CD) task. In experiment 1, muscimol was infused through bilateral cannulae on days 1, 2, and 3 to test the effects of mPFC inactivation on task acquisition and days 19, 20, and 21 to test the effects on retention of the task.

Eyeblink conditioning contingent on hippocampal theta enhances hippocampal and medial prefrontal responses.

Trace eyeblink classical conditioning (tEBCC) can be accelerated by making training trials contingent on the naturally generated hippocampal 3- to 7-Hz theta rhythm. However, it is not well-understood how the presence (or absence) of theta affects stimulus-driven changes within the hippocampus and how it correlates with patterns of neural activity in other essential trace conditioning structures, such as the medial prefrontal cortex (mPFC). In the present study, a brain-computer interface delivered paired or unpaired conditioning trials to rabbits during the explicit presence (T(+)) or absence (T(-)) of theta, yielding significantly faster behavioral learning in the T(+)-paired group.

Spatial representations in dorsal hippocampal neurons during a tactile-visual conditional discrimination task.

Trajectory-dependent coding in dorsal CA1 of hippocampus has been evident in various spatial memory tasks aiming to model episodic memory. Hippocampal neurons are considered to be trajectory-dependent if the neuron has a place field located on an overlapping segment of two trajectories and exhibits a reliable difference in firing rate between the two trajectories. It is unclear whether trajectory-dependent coding in hippocampus is a mechanism used by the rat to solve spatial memory tasks.

Decoding movement trajectories through a T-maze using point process filters applied to place field data from rat hippocampal region CA1.

Firing activity from neural ensembles in rat hippocampus has been previously used to determine an animal's position in an open environment and separately to predict future behavioral decisions. However, a unified statistical procedure to combine information about position and behavior in environments with complex topological features from ensemble hippocampal activity has yet to be described. Here we present a two-stage computational framework that uses point process filters to simultaneously estimate the animal's location and predict future behavior from ensemble neural spiking activity.

Hippocampal response patterns during discriminative eyeblink/jaw movement conditioning in the rabbit.

Rabbits were given concurrent training in eyeblink (EB) and jaw movement (JM) conditioning in which 1 tone predicted an airpuff and another tone predicted water. After 10 days of discrimination training, the animals were given 10 days of reversal training. In the discrimination phase, acquisition of the 2 conditioned responses was not significantly different; however JM discrimination errors were much more frequent than were EB errors.