Amy Griffin | University of Delaware (original) (raw)

Papers by Amy Griffin

Research paper thumbnail of Decoding Movement Trajectories Through a T-Maze Using Point Process Filters Applied to Place Field Data from Rat Hippocampal Region CA1

Http Dx Doi Org 10 1162 Neco 2009 10 08 893, Nov 18, 2010

Research paper thumbnail of In vivo polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) in rodent cerebral cortex

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference, 2011

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

Neurobiology of Learning and Memory, 2015

Inactivation of the rodent medial prefrontal cortex (mPFC) and hippocampus or disconnection of th... more 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. However, it is unknown how delay duration relates to the function of Re/Rh. If Re/Rh are critical in modulating mPFC-hippocampus interactions, inactivation of the RE/Rh should produce a delay-dependent impairment in spatial working memory performance. To investigate this question, groups of rats were trained on one of three different spatial working memory tasks: continuous alternation (CA), delayed alternation with a five-second delay (DA5), or with a thirty-second delay (DA30). The Re/Rh were inactivated with muscimol infusions prior to testing. The results demonstrate that inactivation of RE/Rh produces a deficit only on the two DA tasks, supporting the notion that the Re/Rh is a critical orchestrator of mPFC-HC interactions.

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

Frontiers in systems neuroscience, 2015

Despite decades of research, the neural mechanisms of spatial working memory remain poorly unders... more 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. Oscillatory synchrony between the hippocampus and mPFC has been shown to increase in tasks with high spatial working memory demand. However, the mechanisms and circuitry supporting hippocampal-mPFC interactions during these tasks is unknown. The midline thalamic nucleus reuniens (RE) is reciprocally connected to both the hippocampus and the mPFC and has been shown to be critical for a...

Research paper thumbnail of Hippocampal Signatures of Episodic Memory: Evidence from Single-Unit Recording Studies

Frontiers in Behavioral Neuroscience, 2013

Research paper thumbnail of Gradual Translocation of Spatial Correlates of Neuronal Firing in the Hippocampus toward Prospective Reward Locations

Research paper thumbnail of Spatial Representations of Hippocampal CA1 Neurons Are Modulated by Behavioral Context in a Hippocampus-Dependent Memory Task

Journal of Neuroscience, 2007

Although it is well known that hippocampal neurons code spatial information, it is less clear how... more Although it is well known that hippocampal neurons code spatial information, it is less clear how these spatial representations are influenced by memory demands, especially in hippocampus-dependent tasks. Recently, our laboratory has demonstrated that hippocampal spatial representations are influenced by mnemonic factors in a T-maze continuous alternation task. Another unique experimental approach that might reveal the ways in which task-related factors impact hippocampal spatial representations is to compare firing patterns between events that require distinct episodic memory processes. Therefore, we recorded from CA1 single neurons during a discrete trial delayed-nonmatch-to-place task that allowed within-trial comparison between an encoding (sample) phase and a retrieval (choice) phase. A large subset of neurons that fired on the central stem of the maze showed dramatic selectivity for either the sample or choice phase of the trial. However, surprisingly, there were fewer neurons that showed differential firing rates between left- and right-bound trajectories. Our results suggest that trial-phase-selective coding is common in tasks that require rapid alternation between encoding and retrieval processes.

Research paper thumbnail of Spatial representations in dorsal hippocampal neurons during a tactile-visual conditional discrimination task

Hippocampus, 2012

Trajectory-dependent coding in dorsal CA1 of hippocampus has been evident in various spatial memo... more 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. A first step in answering this question is to compare results between studies using tasks that require spatial working memory and those that do not. We recorded single units from dorsal CA1 of hippocampus during performance of a discrete-trial, tactile-visual conditional discrimination (CD) task in a T-maze. In this task, removable floor inserts that differ in texture and appearance cue the rat to visit either the left or right goal arm to receive a food reward. Our goal was to assess whether trajectory coding would be evident in the CD task. Our results show that trajectory coding was rare in the CD task, with only 12 of 71 cells with place fields on the maze stem showing a significant firing rate difference between left and right trials. For comparison, we recorded from dorsal CA1 during the acquisition and performance of a continuous spatial alternation task identical to that used in previous studies and found a proportion of trajectory coding neurons similar to what has been previously reported. Our data suggest that trajectory coding is not a universal mechanism used by the hippocampus to disambiguate similar trajectories, and instead may be more likely to appear in tasks that require the animal to retrieve information about a past trajectory, particularly in tasks that are continuous rather than discrete in nature.

Research paper thumbnail of Dynamic coding of dorsal hippocampal neurons between tasks that differ in structure and memory demand

Hippocampus, 2013

Hippocampal place fields show remapping between environments that contain sufficiently different ... more 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. A special case of remapping may be trajectory coding, the tendency for hippocampal neurons to exhibit different firing rates depending upon recently visited or upcoming spatial locations. To further delineate the conditions under which different task features elicit remapping, we recorded from place cells in dorsal CA1 of hippocampus while rats switched between tasks that differed in memory demand and task structure; continuous spatial alternation (CA), delayed spatial alternation (DA), and tactile-visual conditional discrimination (CD). Individual hippocampal neurons and populations of simultaneously recorded neurons showed coherent remapping between CA and CD. However, task remapping was rarely seen between DA and CD. Analysis of individual units revealed that even though the population retained a coherent representation of task structure across the DA and CD tasks, the majority of individual neurons consistently remapped at some point during recording sessions. In contrast with previous studies, trajectory coding on the stem of the T-maze was virtually absent during all of the tasks, suggesting that experience with multiple tasks in the same environment reduces the likelihood that hippocampal neurons will represent distinct trajectories. Trajectory coding was, however, observed during the delay period of DA. Whether place fields change in response to task or trial type or remain stable within the same environment may depend on which aspects of the context are most salient or relevant to behavior.

Research paper thumbnail of Nonpharmacological amelioration of age-related learning deficits: The impact of hippocampal  -triggered training

Proceedings of the National Academy of Sciences, 2005

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

Neurobiology of Learning and Memory, 2013

The roles of the dorsal hippocampus (DH) and dorsal striatum (DS) in the learning and retention o... more 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. The performance of two other groups of rats on a previously learned delayed spatial alternation (DA) task was also measured following inactivation of either DS or DH, which allowed us to control for any possibly confounding effects of spatial cues present in the testing room, length of the intertrial interval period on the performance of the CD task, and muscimol on sensorimotor or motivational processing. Muscimol inactivation of dorsal striatum, but not dorsal hippocampus, impaired CD performance, while inactivation of dorsal hippocampus, but not dorsal striatum impaired DA performance. These results demonstrate a double dissociation between the roles of the DH and DS in these two tasks, and provide a systematic characterization of the relationship between these two brain areas and CD performance.

Research paper thumbnail of Inactivation of the Anterior Cingulate Cortex Impairs Extinction of Rabbit Jaw Movement Conditioning and Prevents Extinction-Related Inhibition of Hippocampal Activity

Learning & Memory, 2004

Although past research has highlighted the involvement of limbic structures such as the anterior ... more Although past research has highlighted the involvement of limbic structures such as the anterior cingulate cortex (ACC) and hippocampus in learning, few have addressed the nature of their interaction. The current study of rabbit jaw movement conditioning used a combination of reversible lesions and electrophysiology to examine the involvement of the hippocampus and the ACC during acquisition, performance, and extinction. We found that microinfusions of procaine into the ACC did not significantly alter the rate of behavioral learning or the amplitude of hippocampal conditioned unit responses, but that they disrupted the rhythmic periodicity of conditioned jaw movements. During extinction, whereas controls showed a rapid decline in behavioral CRs and active inhibition of hippocampal unit responses, ACC lesioned rabbits showed a persistence of conditioning-related hippocampal activity and behavioral responding. The results show that the ACC can be important for adaptive suppression of conditioned behavior and suggest a crucial physiological modulation of hippocampus by ACC during extinction.

Research paper thumbnail of Eyeblink conditioning contingent on hippocampal theta enhances hippocampal and medial prefrontal responses

Journal of Neurophysiology, 2011

Trace eyeblink classical conditioning (tEBCC) can be accelerated by making training trials contin... more 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. The stimulus-elicited hippocampal unit responses were larger and more rhythmic in the T(+)-paired group. This facilitation of unit responses was complemented by differences in the hippocampal local field potentials (LFP), with the T(+)-paired group demonstrating more coherent stimulus-evoked theta than T(-)-paired animals and both unpaired groups. mPFC unit responses in the rapid learning T(+)-paired group displayed a clear inhibitory/excitatory sequential pattern of response to the tone that was not seen in any other group. Furthermore, sustained mPFC unit excitation continued through the trace interval in T(+) animals but not in T(-) animals. Thus theta-contingent training is accompanied by 1) acceleration in behavioral learning, 2) enhancement of the hippocampal unit and LFP responses, and 3) enhancement of mPFC unit responses. Together, these data provide evidence that pretrial hippocampal state is related to enhanced neural activity in critical structures of the distributed network supporting the acquisition of tEBCC.

Research paper thumbnail of 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

Journal of Neural Engineering, 2014

After extended implantation times, traditional intracortical neural probes exhibit a foreign-body... more 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. 4 L6-13). The EDOT monomer can be delivered via a microcannula/electrode system into the brain tissue of living animals followed by direct electrochemical polymerization, using the electrode itself as a source of oxidative current. In this study, we investigated the long-term effect of local in vivo PEDOT deposition on hippocampal neural function and histology. Rodent subjects were trained on a hippocampus-dependent task, delayed alternation (DA), and implanted with the microcannula/electrode system in the hippocampus. The animals were divided into four groups with different delay times between the initial surgery and the electrochemical polymerization: (1) control (no polymerization), (2) immediate (polymerization within 5 min of device implantation), (3) early (polymerization within 3-4 weeks after implantation) and (4) late (polymerization 7-8 weeks after polymerization). System impedance at 1 kHz was recorded and the tissue reactions were evaluated by immunohistochemistry. We found that under our deposition conditions, PEDOT typically grew at the tip of the electrode, forming an ∼500 µm cloud in the tissue. This is much larger than the typical width of the glial scar (∼150 µm). After polymerization, the impedance amplitude near the neurologically important frequency of 1 kHz dropped for all the groups; however, there was a time window of 3-4 weeks for an optimal decrease in impedance. For all surgery-polymerization time intervals, the polymerization did not cause significant deficits in performance of the DA task, suggesting that hippocampal function was not impaired by PEDOT deposition. However, GFAP+ and ED-1+ cells were also found at the deposition two weeks after the polymerization, suggesting potential secondary scarring. Therefore, less extensive deposition or milder deposition conditions may be desirable to minimize this scarring while maintaining decreased system impedance.

Research paper thumbnail of Differential mastication kinematics of the rabbit in response to food and water: Implications for conditioned movement

Integrative Physiological & Behavioral Science, 2004

Analysis of naturalistic chewing patterns may provide insight into mapping the neural substrates ... more Analysis of naturalistic chewing patterns may provide insight into mapping the neural substrates of jaw movement control systems, including their adaptive modification during the classically conditioned jaw movement (CJM) paradigm. Here, New Zealand White rabbits were administered food and water stimuli orally to evaluate the influence of stimulus consistency on masticatory pattern. Chewing patterns were recorded via video camera and movements were analyzed by computerized image analysis. The mandibular kinematics, specifically the extent of dorsal/ventral, medial/lateral, and rostral/caudal movement, were significantly larger in food-evoked than water-evoked chewing. Water-evoked chewing frequency, however, was significantly higher than that of food-evoked movements. In light of known cortical mastication modulatory centers, our findings implicate different neural substrates for the responses to food and water stimuli in the rabbit. A detailed delineation of jaw movement patterns and circuitry is essential to characterize the neural substrates of CJM.

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

Behavioural Brain Research, 2013

Research paper thumbnail of Hippocampal response patterns during discriminative eyeblink/jaw movement conditioning in the rabbit

Behavioral Neuroscience, 2008

Rabbits were given concurrent training in eyeblink (EB) and jaw movement (JM) conditioning in whi... more 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. In the reversal phase, correct performance on EB trials increased gradually, as was expected, whereas there was immediate behavioral reversal on JM trials. Differences in size and topography of dorsal CA1 multiple-unit responses reflected the ability of the hippocampus to discriminate between stimuli in trained animals, corresponding to the performance of the behavioral discrimination. During JM trials, the rhythmicity of the neural response was further modulated by the type of the prior trial, suggesting the coding of sequential events by the hippocampus. Thus, hippocampal conditioned activity can rapidly change its magnitude and pattern depending on the specific trial type during a concurrent EB/JM discrimination task and its reversal. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

Research paper thumbnail of Theta-Contingent Trial Presentation Accelerates Learning Rate and Enhances Hippocampal Plasticity During Trace Eyeblink Conditioning

Behavioral Neuroscience, 2004

Hippocampal theta activity has been established as a key predictor of acquisition rate in rabbit ... more Hippocampal theta activity has been established as a key predictor of acquisition rate in rabbit (Orcytolagus cuniculus) classical conditioning. The current study used an online brain--computer interface to administer conditioning trials only in the explicit presence or absence of spontaneous theta activity in the hippocampus-dependent task of trace conditioning. The findings indicate that animals given theta-contingent training learned significantly faster than those given nontheta-contingent training. In parallel with the behavioral results, the theta-triggered group, and not the nontheta-triggered group, exhibited profound increases in hippocampal conditioned unit responses early in training. The results not only suggest that theta-contingent training has a dramatic facilitory effect on trace conditioning but also implicate theta activity in enhancing the plasticity of hippocampal neurons.

Research paper thumbnail of Reversible septal inactivitation disrupts hippocampal slow-wave and unit activity and impairs trace conditioning in rabbits (Oryctolagus cuniculus)

Behavioral Neuroscience, 2002

... & Bland, 1991; for reviews, see Kramis, Vanderwolf, & Bland, 1975; Smythe, Co... more ... & Bland, 1991; for reviews, see Kramis, Vanderwolf, & Bland, 1975; Smythe, Colom, & Bland, 1992; Stewart & Fox, 1990; Wainer et al ... We thank Jason G. Barrera and Steve M. Wold for assistance with data collection and analysis and Zachary Birchmeier for comments on an ...

Research paper thumbnail of Medial septal microinfusion of scopolamine disrupts hippocampal activity and trace jaw movement conditioning

Behavioral Neuroscience, 2000

This study investigated the effects of microinfusion of scopolamine into the medial septum (MS Sc... more This study investigated the effects of microinfusion of scopolamine into the medial septum (MS Scp) on hippocampal neurophysiology and learning of the rabbit's classically conditioned jaw movement response. The percentage of hippocampal theta slow waves (2-8 Hz) decreased after drug infusion in the MS Scp group but did not change in control groups that received infusion of saline into the MS or scopolamine into the cortex. Unit recordings from the MS Scp group showed significantly smaller conditioning-related hippocampal neural responses than seen in controls, and during conditioning, rabbits in the MS Scp group took significantly longer to reach learning criterion than either control group. Thus, the neural and behavioral impairments previously reported for systemic muscarinic blockade were reproduced by microinfusions restricted to the medial septal nucleus.

Research paper thumbnail of Decoding Movement Trajectories Through a T-Maze Using Point Process Filters Applied to Place Field Data from Rat Hippocampal Region CA1

Http Dx Doi Org 10 1162 Neco 2009 10 08 893, Nov 18, 2010

Research paper thumbnail of In vivo polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) in rodent cerebral cortex

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference, 2011

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

Neurobiology of Learning and Memory, 2015

Inactivation of the rodent medial prefrontal cortex (mPFC) and hippocampus or disconnection of th... more 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. However, it is unknown how delay duration relates to the function of Re/Rh. If Re/Rh are critical in modulating mPFC-hippocampus interactions, inactivation of the RE/Rh should produce a delay-dependent impairment in spatial working memory performance. To investigate this question, groups of rats were trained on one of three different spatial working memory tasks: continuous alternation (CA), delayed alternation with a five-second delay (DA5), or with a thirty-second delay (DA30). The Re/Rh were inactivated with muscimol infusions prior to testing. The results demonstrate that inactivation of RE/Rh produces a deficit only on the two DA tasks, supporting the notion that the Re/Rh is a critical orchestrator of mPFC-HC interactions.

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

Frontiers in systems neuroscience, 2015

Despite decades of research, the neural mechanisms of spatial working memory remain poorly unders... more 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. Oscillatory synchrony between the hippocampus and mPFC has been shown to increase in tasks with high spatial working memory demand. However, the mechanisms and circuitry supporting hippocampal-mPFC interactions during these tasks is unknown. The midline thalamic nucleus reuniens (RE) is reciprocally connected to both the hippocampus and the mPFC and has been shown to be critical for a...

Research paper thumbnail of Hippocampal Signatures of Episodic Memory: Evidence from Single-Unit Recording Studies

Frontiers in Behavioral Neuroscience, 2013

Research paper thumbnail of Gradual Translocation of Spatial Correlates of Neuronal Firing in the Hippocampus toward Prospective Reward Locations

Research paper thumbnail of Spatial Representations of Hippocampal CA1 Neurons Are Modulated by Behavioral Context in a Hippocampus-Dependent Memory Task

Journal of Neuroscience, 2007

Although it is well known that hippocampal neurons code spatial information, it is less clear how... more Although it is well known that hippocampal neurons code spatial information, it is less clear how these spatial representations are influenced by memory demands, especially in hippocampus-dependent tasks. Recently, our laboratory has demonstrated that hippocampal spatial representations are influenced by mnemonic factors in a T-maze continuous alternation task. Another unique experimental approach that might reveal the ways in which task-related factors impact hippocampal spatial representations is to compare firing patterns between events that require distinct episodic memory processes. Therefore, we recorded from CA1 single neurons during a discrete trial delayed-nonmatch-to-place task that allowed within-trial comparison between an encoding (sample) phase and a retrieval (choice) phase. A large subset of neurons that fired on the central stem of the maze showed dramatic selectivity for either the sample or choice phase of the trial. However, surprisingly, there were fewer neurons that showed differential firing rates between left- and right-bound trajectories. Our results suggest that trial-phase-selective coding is common in tasks that require rapid alternation between encoding and retrieval processes.

Research paper thumbnail of Spatial representations in dorsal hippocampal neurons during a tactile-visual conditional discrimination task

Hippocampus, 2012

Trajectory-dependent coding in dorsal CA1 of hippocampus has been evident in various spatial memo... more 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. A first step in answering this question is to compare results between studies using tasks that require spatial working memory and those that do not. We recorded single units from dorsal CA1 of hippocampus during performance of a discrete-trial, tactile-visual conditional discrimination (CD) task in a T-maze. In this task, removable floor inserts that differ in texture and appearance cue the rat to visit either the left or right goal arm to receive a food reward. Our goal was to assess whether trajectory coding would be evident in the CD task. Our results show that trajectory coding was rare in the CD task, with only 12 of 71 cells with place fields on the maze stem showing a significant firing rate difference between left and right trials. For comparison, we recorded from dorsal CA1 during the acquisition and performance of a continuous spatial alternation task identical to that used in previous studies and found a proportion of trajectory coding neurons similar to what has been previously reported. Our data suggest that trajectory coding is not a universal mechanism used by the hippocampus to disambiguate similar trajectories, and instead may be more likely to appear in tasks that require the animal to retrieve information about a past trajectory, particularly in tasks that are continuous rather than discrete in nature.

Research paper thumbnail of Dynamic coding of dorsal hippocampal neurons between tasks that differ in structure and memory demand

Hippocampus, 2013

Hippocampal place fields show remapping between environments that contain sufficiently different ... more 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. A special case of remapping may be trajectory coding, the tendency for hippocampal neurons to exhibit different firing rates depending upon recently visited or upcoming spatial locations. To further delineate the conditions under which different task features elicit remapping, we recorded from place cells in dorsal CA1 of hippocampus while rats switched between tasks that differed in memory demand and task structure; continuous spatial alternation (CA), delayed spatial alternation (DA), and tactile-visual conditional discrimination (CD). Individual hippocampal neurons and populations of simultaneously recorded neurons showed coherent remapping between CA and CD. However, task remapping was rarely seen between DA and CD. Analysis of individual units revealed that even though the population retained a coherent representation of task structure across the DA and CD tasks, the majority of individual neurons consistently remapped at some point during recording sessions. In contrast with previous studies, trajectory coding on the stem of the T-maze was virtually absent during all of the tasks, suggesting that experience with multiple tasks in the same environment reduces the likelihood that hippocampal neurons will represent distinct trajectories. Trajectory coding was, however, observed during the delay period of DA. Whether place fields change in response to task or trial type or remain stable within the same environment may depend on which aspects of the context are most salient or relevant to behavior.

Research paper thumbnail of Nonpharmacological amelioration of age-related learning deficits: The impact of hippocampal  -triggered training

Proceedings of the National Academy of Sciences, 2005

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

Neurobiology of Learning and Memory, 2013

The roles of the dorsal hippocampus (DH) and dorsal striatum (DS) in the learning and retention o... more 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. The performance of two other groups of rats on a previously learned delayed spatial alternation (DA) task was also measured following inactivation of either DS or DH, which allowed us to control for any possibly confounding effects of spatial cues present in the testing room, length of the intertrial interval period on the performance of the CD task, and muscimol on sensorimotor or motivational processing. Muscimol inactivation of dorsal striatum, but not dorsal hippocampus, impaired CD performance, while inactivation of dorsal hippocampus, but not dorsal striatum impaired DA performance. These results demonstrate a double dissociation between the roles of the DH and DS in these two tasks, and provide a systematic characterization of the relationship between these two brain areas and CD performance.

Research paper thumbnail of Inactivation of the Anterior Cingulate Cortex Impairs Extinction of Rabbit Jaw Movement Conditioning and Prevents Extinction-Related Inhibition of Hippocampal Activity

Learning & Memory, 2004

Although past research has highlighted the involvement of limbic structures such as the anterior ... more Although past research has highlighted the involvement of limbic structures such as the anterior cingulate cortex (ACC) and hippocampus in learning, few have addressed the nature of their interaction. The current study of rabbit jaw movement conditioning used a combination of reversible lesions and electrophysiology to examine the involvement of the hippocampus and the ACC during acquisition, performance, and extinction. We found that microinfusions of procaine into the ACC did not significantly alter the rate of behavioral learning or the amplitude of hippocampal conditioned unit responses, but that they disrupted the rhythmic periodicity of conditioned jaw movements. During extinction, whereas controls showed a rapid decline in behavioral CRs and active inhibition of hippocampal unit responses, ACC lesioned rabbits showed a persistence of conditioning-related hippocampal activity and behavioral responding. The results show that the ACC can be important for adaptive suppression of conditioned behavior and suggest a crucial physiological modulation of hippocampus by ACC during extinction.

Research paper thumbnail of Eyeblink conditioning contingent on hippocampal theta enhances hippocampal and medial prefrontal responses

Journal of Neurophysiology, 2011

Trace eyeblink classical conditioning (tEBCC) can be accelerated by making training trials contin... more 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. The stimulus-elicited hippocampal unit responses were larger and more rhythmic in the T(+)-paired group. This facilitation of unit responses was complemented by differences in the hippocampal local field potentials (LFP), with the T(+)-paired group demonstrating more coherent stimulus-evoked theta than T(-)-paired animals and both unpaired groups. mPFC unit responses in the rapid learning T(+)-paired group displayed a clear inhibitory/excitatory sequential pattern of response to the tone that was not seen in any other group. Furthermore, sustained mPFC unit excitation continued through the trace interval in T(+) animals but not in T(-) animals. Thus theta-contingent training is accompanied by 1) acceleration in behavioral learning, 2) enhancement of the hippocampal unit and LFP responses, and 3) enhancement of mPFC unit responses. Together, these data provide evidence that pretrial hippocampal state is related to enhanced neural activity in critical structures of the distributed network supporting the acquisition of tEBCC.

Research paper thumbnail of 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

Journal of Neural Engineering, 2014

After extended implantation times, traditional intracortical neural probes exhibit a foreign-body... more 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. 4 L6-13). The EDOT monomer can be delivered via a microcannula/electrode system into the brain tissue of living animals followed by direct electrochemical polymerization, using the electrode itself as a source of oxidative current. In this study, we investigated the long-term effect of local in vivo PEDOT deposition on hippocampal neural function and histology. Rodent subjects were trained on a hippocampus-dependent task, delayed alternation (DA), and implanted with the microcannula/electrode system in the hippocampus. The animals were divided into four groups with different delay times between the initial surgery and the electrochemical polymerization: (1) control (no polymerization), (2) immediate (polymerization within 5 min of device implantation), (3) early (polymerization within 3-4 weeks after implantation) and (4) late (polymerization 7-8 weeks after polymerization). System impedance at 1 kHz was recorded and the tissue reactions were evaluated by immunohistochemistry. We found that under our deposition conditions, PEDOT typically grew at the tip of the electrode, forming an ∼500 µm cloud in the tissue. This is much larger than the typical width of the glial scar (∼150 µm). After polymerization, the impedance amplitude near the neurologically important frequency of 1 kHz dropped for all the groups; however, there was a time window of 3-4 weeks for an optimal decrease in impedance. For all surgery-polymerization time intervals, the polymerization did not cause significant deficits in performance of the DA task, suggesting that hippocampal function was not impaired by PEDOT deposition. However, GFAP+ and ED-1+ cells were also found at the deposition two weeks after the polymerization, suggesting potential secondary scarring. Therefore, less extensive deposition or milder deposition conditions may be desirable to minimize this scarring while maintaining decreased system impedance.

Research paper thumbnail of Differential mastication kinematics of the rabbit in response to food and water: Implications for conditioned movement

Integrative Physiological & Behavioral Science, 2004

Analysis of naturalistic chewing patterns may provide insight into mapping the neural substrates ... more Analysis of naturalistic chewing patterns may provide insight into mapping the neural substrates of jaw movement control systems, including their adaptive modification during the classically conditioned jaw movement (CJM) paradigm. Here, New Zealand White rabbits were administered food and water stimuli orally to evaluate the influence of stimulus consistency on masticatory pattern. Chewing patterns were recorded via video camera and movements were analyzed by computerized image analysis. The mandibular kinematics, specifically the extent of dorsal/ventral, medial/lateral, and rostral/caudal movement, were significantly larger in food-evoked than water-evoked chewing. Water-evoked chewing frequency, however, was significantly higher than that of food-evoked movements. In light of known cortical mastication modulatory centers, our findings implicate different neural substrates for the responses to food and water stimuli in the rabbit. A detailed delineation of jaw movement patterns and circuitry is essential to characterize the neural substrates of CJM.

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

Behavioural Brain Research, 2013

Research paper thumbnail of Hippocampal response patterns during discriminative eyeblink/jaw movement conditioning in the rabbit

Behavioral Neuroscience, 2008

Rabbits were given concurrent training in eyeblink (EB) and jaw movement (JM) conditioning in whi... more 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. In the reversal phase, correct performance on EB trials increased gradually, as was expected, whereas there was immediate behavioral reversal on JM trials. Differences in size and topography of dorsal CA1 multiple-unit responses reflected the ability of the hippocampus to discriminate between stimuli in trained animals, corresponding to the performance of the behavioral discrimination. During JM trials, the rhythmicity of the neural response was further modulated by the type of the prior trial, suggesting the coding of sequential events by the hippocampus. Thus, hippocampal conditioned activity can rapidly change its magnitude and pattern depending on the specific trial type during a concurrent EB/JM discrimination task and its reversal. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

Research paper thumbnail of Theta-Contingent Trial Presentation Accelerates Learning Rate and Enhances Hippocampal Plasticity During Trace Eyeblink Conditioning

Behavioral Neuroscience, 2004

Hippocampal theta activity has been established as a key predictor of acquisition rate in rabbit ... more Hippocampal theta activity has been established as a key predictor of acquisition rate in rabbit (Orcytolagus cuniculus) classical conditioning. The current study used an online brain--computer interface to administer conditioning trials only in the explicit presence or absence of spontaneous theta activity in the hippocampus-dependent task of trace conditioning. The findings indicate that animals given theta-contingent training learned significantly faster than those given nontheta-contingent training. In parallel with the behavioral results, the theta-triggered group, and not the nontheta-triggered group, exhibited profound increases in hippocampal conditioned unit responses early in training. The results not only suggest that theta-contingent training has a dramatic facilitory effect on trace conditioning but also implicate theta activity in enhancing the plasticity of hippocampal neurons.

Research paper thumbnail of Reversible septal inactivitation disrupts hippocampal slow-wave and unit activity and impairs trace conditioning in rabbits (Oryctolagus cuniculus)

Behavioral Neuroscience, 2002

... & Bland, 1991; for reviews, see Kramis, Vanderwolf, & Bland, 1975; Smythe, Co... more ... & Bland, 1991; for reviews, see Kramis, Vanderwolf, & Bland, 1975; Smythe, Colom, & Bland, 1992; Stewart & Fox, 1990; Wainer et al ... We thank Jason G. Barrera and Steve M. Wold for assistance with data collection and analysis and Zachary Birchmeier for comments on an ...

Research paper thumbnail of Medial septal microinfusion of scopolamine disrupts hippocampal activity and trace jaw movement conditioning

Behavioral Neuroscience, 2000

This study investigated the effects of microinfusion of scopolamine into the medial septum (MS Sc... more This study investigated the effects of microinfusion of scopolamine into the medial septum (MS Scp) on hippocampal neurophysiology and learning of the rabbit's classically conditioned jaw movement response. The percentage of hippocampal theta slow waves (2-8 Hz) decreased after drug infusion in the MS Scp group but did not change in control groups that received infusion of saline into the MS or scopolamine into the cortex. Unit recordings from the MS Scp group showed significantly smaller conditioning-related hippocampal neural responses than seen in controls, and during conditioning, rabbits in the MS Scp group took significantly longer to reach learning criterion than either control group. Thus, the neural and behavioral impairments previously reported for systemic muscarinic blockade were reproduced by microinfusions restricted to the medial septal nucleus.