General Background
Human and nonhuman animals are dynamic creatures, constantly striving to behave adaptively in an ever-changing environment. I studied some of the mechanisms by which an animal might learn and remember complex information, especially that which is organized spatially or temporally. My earlier research investigated the effect of (high-fat) diet on hippocampal-dependent learning and memory. This issue still interests me, although is no longer manifested in my empirical work.
My experimental design and general empirical approach benefit from my graduate training in learning theory-- using classical, operant, and instrumental conditioning paradigms to understand complex processes.
Human and nonhuman animals are dynamic creatures, constantly striving to behave adaptively in an ever-changing environment. I studied some of the mechanisms by which an animal might learn and remember complex information, especially that which is organized spatially or temporally. My earlier research investigated the effect of (high-fat) diet on hippocampal-dependent learning and memory. This issue still interests me, although is no longer manifested in my empirical work.
My experimental design and general empirical approach benefit from my graduate training in learning theory-- using classical, operant, and instrumental conditioning paradigms to understand complex processes.
Recent Research
I recently completed a post-doctoral fellowship in the Fortin Lab at UC Irvine, which investigates the neurobiological mechanisms underlying the memory for sequences of items and the memory for elapsed time.
I worked to provide preliminary data on the neural mechanisms underlying age-related cognitive impairments in the memory for sequences of items in rats, with multi-site electrophysiological recordings and subsequent therapeutic drug administration. In mid-November (2017), this work was presented at the annual Society for Neuroscience conference, which was held in Washington D.C. (poster title and abstract provided below).
Additionally, my time in the laboratory was spent developing a novel protocol and providing preliminary data on the use of designer receptors exclusively activated by designer drugs (DREADDs) to test the role of hippocampal subregion CA3 in the memory for sequences of items in rats. In mid-November (2016), I presented my recent work at the annual Society for Neuroscience conference, which was held in San Diego, California (poster title and abstract provided below).
I recently completed a post-doctoral fellowship in the Fortin Lab at UC Irvine, which investigates the neurobiological mechanisms underlying the memory for sequences of items and the memory for elapsed time.
I worked to provide preliminary data on the neural mechanisms underlying age-related cognitive impairments in the memory for sequences of items in rats, with multi-site electrophysiological recordings and subsequent therapeutic drug administration. In mid-November (2017), this work was presented at the annual Society for Neuroscience conference, which was held in Washington D.C. (poster title and abstract provided below).
Additionally, my time in the laboratory was spent developing a novel protocol and providing preliminary data on the use of designer receptors exclusively activated by designer drugs (DREADDs) to test the role of hippocampal subregion CA3 in the memory for sequences of items in rats. In mid-November (2016), I presented my recent work at the annual Society for Neuroscience conference, which was held in San Diego, California (poster title and abstract provided below).
2017 Society for Neuroscience Conference (Washington D.C.)
Poster Title
Age-associated changes in sequence memory performance and multiregional local field potential synchrony in rats
Poster Abstract
Temporal organization is a defining feature of episodic memory, as the memory for individual events includes information about when they occurred. In particular, the ability to remember sequential relationships among events or stimuli is shared by a variety of species, including humans, nonhuman primates, and rodents. Our laboratory has developed and validated a nonspatial cross-species paradigm to investigate the neural basis of sequence memory in humans and rats. Using this paradigm, in collaboration with a human neuroimaging laboratory, we previously demonstrated significant impairments in sequence memory performance in older adult humans. In particular, relative to young controls, older participants showed poorer overall performance as well as a specific pattern of impairments across probe types. Critically, providing a comparable behavioral characterization in older rats is important for investigating the neural mechanisms underlying this age-associated memory impairment as well as offering a platform for testing the effects of potential therapeutics. To test the hypothesis that a similar pattern of age-associated impairments is present in rats, we tested young and aged rats (pre-screened for spatial memory impairment in the Morris water maze) in our nonspatial (olfactory) sequence memory task. We observed similar results as previously reported in humans, such that aged subjects showed poorer overall performance, with a specific pattern of impairments across probe types, the severity of which was associated with their pre-screened spatial impairments. In order to probe the underlying neural mechanisms, ongoing efforts focus on recording local field potential (LFP) activity from multiple regions as the same subjects perform the task, to test the hypothesis that the observed age-related behavioral impairments are associated with a reduction in LFP synchrony among hippocampal, entorhinal, and prefrontal subregions.
Poster Title
Age-associated changes in sequence memory performance and multiregional local field potential synchrony in rats
Poster Abstract
Temporal organization is a defining feature of episodic memory, as the memory for individual events includes information about when they occurred. In particular, the ability to remember sequential relationships among events or stimuli is shared by a variety of species, including humans, nonhuman primates, and rodents. Our laboratory has developed and validated a nonspatial cross-species paradigm to investigate the neural basis of sequence memory in humans and rats. Using this paradigm, in collaboration with a human neuroimaging laboratory, we previously demonstrated significant impairments in sequence memory performance in older adult humans. In particular, relative to young controls, older participants showed poorer overall performance as well as a specific pattern of impairments across probe types. Critically, providing a comparable behavioral characterization in older rats is important for investigating the neural mechanisms underlying this age-associated memory impairment as well as offering a platform for testing the effects of potential therapeutics. To test the hypothesis that a similar pattern of age-associated impairments is present in rats, we tested young and aged rats (pre-screened for spatial memory impairment in the Morris water maze) in our nonspatial (olfactory) sequence memory task. We observed similar results as previously reported in humans, such that aged subjects showed poorer overall performance, with a specific pattern of impairments across probe types, the severity of which was associated with their pre-screened spatial impairments. In order to probe the underlying neural mechanisms, ongoing efforts focus on recording local field potential (LFP) activity from multiple regions as the same subjects perform the task, to test the hypothesis that the observed age-related behavioral impairments are associated with a reduction in LFP synchrony among hippocampal, entorhinal, and prefrontal subregions.
2016 Society for Neuroscience Conference (San Diego, California)
Poster Title
Using DREADDs to compare the effects of inactivating CA3 versus the CA3-CA1 projection on the memory for sequences of events.
Poster Abstract
The ability to temporally organize information is fundamental to many perceptual, cognitive, and motor processes. Temporal organization is also a defining feature of episodic memory, as the memory for individual events includes information about when they occurred. In particular, the ability to remember sequential relationships among events or stimuli is shared by a variety of species including humans, non-human primates, and rodents.
Our laboratory has recently developed and validated a cross-species paradigm to test nonspatial sequential memory; recent work using this approach has demonstrated that the hippocampus plays a critical role in this ability. Notably, whole hippocampal inactivations produce substantial deficits in the memory for a sequence of items (Allen et al., in prep.), and electrophysiological recordings show that dorsal CA1 neurons discriminate the temporal context in which items are presented (Allen et al., 2016). In particular, such neurons fire differentially to odors depending on whether they were presented in sequence or out of sequence.
Here, we aim to further investigate the specific hippocampal circuitry supporting this form of sequence memory and, specifically, the role of subregion CA3. Computational models suggest that CA3 may be particularly well-suited to code for sequential relationships among items because of its high degree of recurrent connections. To test this hypothesis, we compared the effects of whole CA3 inactivation to specific CA3-CA1 projection inactivation using designer receptors exclusively activated by designer drugs (DREADDs).
Subjects consisted of ten Long-Evans rats, who underwent bilateral infusions of either AAV9 (experimental virus) or rAAV8 (control virus) into dorsal CA3, as well as bilateral implantation of guide cannulae into dorsal CA1. After reaching criterion in the olfactory sequence memory task, neuronal inactivation is induced by clozapine-N-oxide (CNO) injections, with phosphate-buffered saline (PBS) as a control. Systemic CNO injections inactivate the entire CA3 subregion, whereas local infusions specifically block CA3-CA1 communication. This approach allows for testing the general contribution of CA3 as well as the specific role of the CA3-CA1 pathway in the ability to remember a sequence of items.
Poster Title
Using DREADDs to compare the effects of inactivating CA3 versus the CA3-CA1 projection on the memory for sequences of events.
Poster Abstract
The ability to temporally organize information is fundamental to many perceptual, cognitive, and motor processes. Temporal organization is also a defining feature of episodic memory, as the memory for individual events includes information about when they occurred. In particular, the ability to remember sequential relationships among events or stimuli is shared by a variety of species including humans, non-human primates, and rodents.
Our laboratory has recently developed and validated a cross-species paradigm to test nonspatial sequential memory; recent work using this approach has demonstrated that the hippocampus plays a critical role in this ability. Notably, whole hippocampal inactivations produce substantial deficits in the memory for a sequence of items (Allen et al., in prep.), and electrophysiological recordings show that dorsal CA1 neurons discriminate the temporal context in which items are presented (Allen et al., 2016). In particular, such neurons fire differentially to odors depending on whether they were presented in sequence or out of sequence.
Here, we aim to further investigate the specific hippocampal circuitry supporting this form of sequence memory and, specifically, the role of subregion CA3. Computational models suggest that CA3 may be particularly well-suited to code for sequential relationships among items because of its high degree of recurrent connections. To test this hypothesis, we compared the effects of whole CA3 inactivation to specific CA3-CA1 projection inactivation using designer receptors exclusively activated by designer drugs (DREADDs).
Subjects consisted of ten Long-Evans rats, who underwent bilateral infusions of either AAV9 (experimental virus) or rAAV8 (control virus) into dorsal CA3, as well as bilateral implantation of guide cannulae into dorsal CA1. After reaching criterion in the olfactory sequence memory task, neuronal inactivation is induced by clozapine-N-oxide (CNO) injections, with phosphate-buffered saline (PBS) as a control. Systemic CNO injections inactivate the entire CA3 subregion, whereas local infusions specifically block CA3-CA1 communication. This approach allows for testing the general contribution of CA3 as well as the specific role of the CA3-CA1 pathway in the ability to remember a sequence of items.
