Biology subjects

Bladon, J. H.

Publications and source records attributed to Bladon, J. H..

7 recordsLinked to original sources

bioRxiv2025

Cooperative behavior guided by peer coordination is impaired in a Fragile-X rat model of autism

Cooperative behavior, the ability of individuals to coordinate their actions toward shared goals, is fundamental to survival and social success across species. However, the mechanisms supporting cooperation and how their disruption leads to social deficits in neurodevelopmental disorders such as autism spectrum disorder (ASD), remain poorly understood. To address these questions, we developed a novel cooperation task in paired spatial mazes under deterministic (100%) and probabilistic (50%) reward contingencies, utilizing dyads of littermate wild-type (WT) and Fmr1 knockout (Fmr1) rats, a model of Fragile X syndrome. Both WT and Fmr1 rat pairs exhibited dynamic turn-taking with mixed leader-follower behavior for cooperation; however, WT pairs achieved significantly greater cooperation success than Fmr1 pairs. WT and Fmr1 pairs both successfully utilized a simple follower-tracking-leader reactive strategy, dependent on partner-directed visual attention, resulting in slower asynchronous transitions, with Fmr1 pairs more reliant on this strategy. WT rat pairs in addition exhibited a more efficient, flexible predictive cooperation strategy, dependent on coordination of optimal transition patterns between rat pairs and recent partner choice history, resulting in faster synchronous transitions. Fmr1 rats were unable to show adaptation to the probabilistic reward condition by employing this more efficient social reciprocity strategy of higher complexity, leading to deficits in cooperative behavior. These findings reveal key behavioral strategies of varying complexity for cooperation, reveal the specific disruption of complex social reciprocity strategies in a rat ASD model, and provide a foundation for investigation of social interactions and underlying neural mechanisms in cooperative decision-making with relevance to neurodevelopmental disorders.

neuroscience↗

bioRxiv2023

Hippocampal engrams generate flexible behavioral responses and brain-wide network states

Memory engrams are both necessary and sufficient to mediate behavioral outputs. Defensive behaviors such as freezing and avoidance are commonly examined during hippocampal-mediated fear engram reactivation, yet how reactivation of these cellular populations across different contexts engages the brain to produce a variety of defensive behaviors is relatively unclear. To address this, we first optogenetically reactivated a tagged fear engram in the dentate gyrus (DG) subregion of the hippocampus across three distinct contexts. We found that there were differential amounts of light-induced freezing depending on the size of the context in which reactivation occurred: mice demonstrated robust light-induced freezing in the most spatially restricted of the three contexts but not in the largest. We then utilized graph theoretical analyses to identify brain-wide alterations in cFos co-activation during engram reactivation across the smallest and largest contexts. Our manipulations conferred greater positive cFos correlations and recruited regions spanning putative fear and defense systems as hubs in the respective networks. Moreover, reactivating DG-mediated engrams generated network topologies across experimental conditions, emphasizing both shared and distinct features. By identifying and manipulating the circuits supporting memory function, as well as their corresponding brain-wide activity patterns, it is thereby possible to resolve systems-level biological mechanisms mediating memorys capacity to modulate behavioral states. SIGNIFICANCE STATEMENTImplementing appropriate defensive behaviors across disparate environments is essential for survival. Memories can be used to select these responses. Recent work identified and artificially manipulated cellular ensembles within the hippocampus that mediate fear memory recall, yet how these populations engage brain-wide pathways that mediate defensive behaviors under environmental contingencies is unclear. We demonstrated here that reactivation across environments of various sizes elicits different behavioral responses and corresponding brain-wide network dynamics. These findings establish the flexibility of memory-bearing ensembles in generating brain and behavior states.

neuroscience↗

bioRxiv2021

Internally Generated Time in the Rodent Hippocampus is Logarithmically Compressed

The Weber-Fechner law proposes that our perceived sensory input increases with physical input on a logarithmic scale. Hippocampal "time cells" carry a record of recent experience by firing sequentially during a circumscribed period of time after a triggering stimulus. Different cells have "time fields" at different delays up to at least tens of seconds. Past studies suggest that time cells represent a compressed timeline by demonstrating that fewer time cells fire late in the delay and their time fields are wider. This paper asks whether the compression of time cells obeys the Weber-Fechner Law. Time cells were studied with a hierarchical Bayesian model that simultaneously accounts for the firing pattern at the trial level, cell level, and population level. This procedure allows separate estimates of the within-trial receptive field width and the across-trial variability. After isolating across-trial variability, time field width increased linearly with delay. Further, the time cell population was distributed evenly along a logarithmic time axis. These findings provide strong quantitative evidence that the neural temporal representation in rodent hippocampus is logarithmically compressed and obeys a neural Weber-Fechner Law.

neuroscience↗

bioRxiv2021

Reactivating Hippocampal-Mediated Memories to Disrupt the Reconsolidation of Fear

Memories are stored in the brain as cellular ensembles activated during learning and reactivated during retrieval. Using the Tet-tag system in mice, we label dorsal dentate gyrus neurons activated by positive, neutral or negative experiences with channelrhodopsin-2. Following fear-conditioning, these cells are artificially reactivated during fear memory recall. Optical stimulation of a competing positive memory is sufficient to update the memory during reconsolidation, thereby reducing conditioned fear acutely and enduringly. Moreover, mice demonstrate operant responding for reactivation of a positive memory, confirming its rewarding properties. These results show that interference from a rewarding experience can counteract negative affective states. While memory-updating, induced by memory reactivation, involves a relatively small set of neurons, we also find that activating a large population of randomly labeled dorsal dentate gyrus neurons is effective in promoting reconsolidation. Importantly, memory-updating is specific to the fear memory. These findings implicate the dorsal dentate gyrus as a potential therapeutic node for modulating memories to suppress fear.

neuroscience↗

bioRxiv2021

Adaptable and Automated Rodent Behavior Maze System

Mazes are a fundamental and widespread tool in behavior and systems neuroscience research in rodents, especially in spatial navigation and spatial memory investigations in freely behaving animals. However, their form and inflexibility often restrict potential experimental paradigms that involve multiple or adaptive maze designs. Unique layouts often lead to elevated costs, whether financially or in terms of time investment from scientists. To alleviate these issues, we have developed an automated, modular maze system that is flexible and scalable. This open source Adapt-A-Maze (AAM) system will allow for experiments with multiple track configurations in rapid succession. Additionally, the flexibility can expedite prototyping of behavioral paradigms. Automation ensures less variability in experimental parameters and higher throughput. Finally, the standardized componentry enhances experimental repeatability within labs and replicability across labs. Our maze was successfully used across labs, in multiple experimental designs, with and without extracellular or optical recordings, in rats. The AAM system presents multiple advantages over current maze options and can facilitate novel behavior and systems neuroscience research. Significance statementWe have developed an open source, modular maze system (the Adapt-A-Maze, AAM) that enables any lab interested in rodent behavior and cognition to create standard and unique mazes for their research. The AAM uses modular track pieces that can be combined to create a wide array of maze types. The AAM system also included reward wells with lick detection and pneumatic barriers. All aspects of the maze can be controlled via TTL signals to automate tasks and improve repeatability of experiments. The AAM system is expected to help labs quickly and inexpensively set up recordable experiments to advance our understanding of the neurophysiology underlying behavior and cognition.

neuroscience↗

bioRxiv2020

Neural coordination mechanisms for associative memory recall and decision making in the hippocampal-prefrontal network

Memory-guided decision making involves long-range coordination across sensory and cognitive brain networks, with key roles for the hippocampus and prefrontal cortex (PFC). To investigate these coordination mechanisms, we monitored activity in hippocampus (CA1), PFC, and olfactory bulb in rats performing an odor-place associative memory guided decision task on a T-maze. During odor sampling, the beta (20-30 Hz) and respiratory (7-8 Hz) rhythms (RR) were prominent across the three regions, with CA1-PFC beta and RR coherence enhanced during the odor-cued decision making period. Beta phase modulation of CA1 and PFC neuronal activity during this period was linked to accurate decisions, suggesting that this temporal modulation influences sensory-cued decision making. Single neurons and ensembles in both CA1 and PFC encoded and predicted animals upcoming choices. Our findings indicate that rhythmic coordination within the hippocampal-prefrontal network supports utilization of odor cues for memory-guided decision making.

neuroscience↗

bioRxiv2018

In a temporally segmented experience hippocampal neurons represent temporally drifting context but not discrete segments.

There is widespread agreement that episodic memory is organized into a timeline of past experiences. Recent work suggests that the hippocampus may parse the flow of experience into discrete episodes separated by event boundaries. A complementary body of work suggests that context changes gradually as experience unfolds. We recorded from hippocampal neurons as male long evans rats performed 6 blocks of an object discrimination task in sets of 15 trials. Each block was separated by removal from the testing chamber for a delay to enable segmentation. The reward contingency reversed from one block to the next to incentivize segmentation. We expected animals to hold two distinct, recurring representations of context to match the two distinct rule contingencies. Instead, we found that overtrained rats began each block neither above nor below chance but by guessing randomly. While many units had clear firing fields selective to the conjunction of objects in places, a significant population also reflected a continuously drifting code both within block and across blocks. Despite clear boundaries between blocks, we saw no neural evidence for event segmentation in this experiment. Rather, the hippocampal ensemble drifted continuously across time. This continuous drift in the neural representation was consistent with the lack of segmentation observed in behavior.\n\nSignificance StatementThe neuroscience literature yet to reach consensus as to how hippocampal firing fields support the organizing of events across time in episodic memory. Initial reports of hippocampal activity focused on discrete episodes within which representations were stable, and across which representations remapped. However, it remains unclear whether this segmentation of representations is merely an artifact of cue responsivity. More recently, research has shown that a proportion of the population codes for temporal aspects of context by exhibiting varying degrees of drift in their firing fields. Drift is hypothesized to represent a continually evolving temporal context, however it is unclear whether this drift is continuous or is also a mere artifact of changing experiences. We recorded from the dorsal hippocampus of rats performing an object discrimination task that involved contexts that were segmented in time. Overtrained rats were unable to anticipate the identity of the upcoming context, but may have used context boundaries to their advantage. Event segmentation theory predicts that hippocampal ensembles would alternate between behaviorally-relevant segments. Contrary to these predictions, animals showed weak evidence of context segmentation, even across blocks with different reward contingencies. Hippocampal ensembles showed neither evidence of alternating between stable contexts nor sensitivity to context boundaries, but did show robust temporal drift.

animal behavior and cognition↗