Biology subjects

Freeman, J. H.

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

4 recordsLinked to original sources

bioRxiv2026

Lateral Cerebellar Nucleus Lesions Disrupt Rule-Based Category Learning and Cognitive Flexibility in Rats

Cerebellar communication with the prefrontal cortex (PFC) may play a significant role in cognitive functions. Our previous studies found that rule-based (RB) category learning depends on the PFC in humans and rats. The PFC is also crucial for behavioral flexibility following rule-changes in various tasks. Very little is known regarding the role of the cerebellum in RB category learning. The current study was designed to determine whether the cerebellum plays a role in RB category learning, and in categorization following a rule switch. Female and male rats were given bilateral lesions of the lateral cerebellar nuclei (LCN) or a control surgery and trained on an RB category learning task followed by a category rule switch. A subset of rats was trained on a control discrimination task with the same trial procedures as the categorization task. Rats with LCN lesions took significantly longer to learn both the first and second category rules but were not impaired on the control task. Computational modeling revealed less task engagement and increased switching between engaged and non-engaged states in the LCN lesion group. Several measures of task performance indicated that the category learning deficit was not caused by a motor impairment, response bias, or an inability to discriminate the stimuli. The category learning deficits with LCN lesions were related to reduced accuracy of stimulus classification, an inability to maintain task engagement, and loss of flexibility. The results show, for the first time, that the cerebellum plays a crucial role in category learning and category rule-switching.

neuroscience↗

bioRxiv2025

Interactions between the medial prefrontal cortex, dorsomedial striatum, and dorsal hippocampus that support rat category learning

Categorization creates memory representations that are efficient, generalizable, and robust to noise. Multiple brain regions have been implicated in categorization, including the prefrontal cortex, striatum, and hippocampus; however, few studies have examined how these regions interact during category learning. We recorded neural activity in the medial prefrontal cortex (PFC), dorsomedial striatum (DMS), and dorsal hippocampus (HPC) while rats learned to categorize distributions of visual stimuli. We found a learning-related shift in contributions from the PFC (with DMS[->]PFC theta (4-10Hz) interactions) to the HPC (with HPC[->]DMS and bidirectional PFC-HPC theta interactions). Decision-making depended on DMS and HPC spiking, as well as the PFC[->]HPC[->]DMS pathway. Our results provide a framework that characterizes how the PFC-DMS-HPC network interacts during category learning. This is informative for multiple neurological disorders that affect category learning, including Parkinsons Disease, autism, and dementia. Highlights- Rats learned to categorize distributions of visual stimuli. - Early training sessions relied on PFC spiking and DMS[->]PFC theta interactions. - After learning, contributions shifted to HPC spiking, HPC[->]DMS interactions, and bidirectional PFC-HPC interactions. - Decision-making depended on DMS and HPC spiking and PFC[->]HPC[->]DMS interactions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=180 HEIGHT=200 SRC="FIGDIR/small/649785v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@ba3342org.highwire.dtl.DTLVardef@7b62a4org.highwire.dtl.DTLVardef@890676org.highwire.dtl.DTLVardef@75f84_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

The dorsal hippocampus' role in context-based timing in rodents

To act proactively, we must predict when future events will occur. Individuals generate temporal predictions using cues that indicate an event will happen after a certain duration elapses. Neural models of timing focus on how the brain represents these cue-duration associations. However, these models often overlook the fact that situational factors frequently modulate temporal expectations. For example, in realistic environments, the intervals associated with different cues will often covary due to a common underlying cause. According to the common cause hypothesis, observers anticipate this covariance such that, when one cues interval changes, temporal expectations for other cues shift in the same direction. Furthermore, as conditions will often differ across environments, the same cue can mean different things in different contexts. Therefore, updates to temporal expectations should be context-specific. Behavioral work supports these predictions, yet their underlying neural mechanisms are unclear. Here, we asked whether the dorsal hippocampus mediates context-based timing, given its broad role in context-conditioning. Specifically, we trained rats with either hippocampal or sham lesions that two cues predicted reward after either a short or long duration elapsed (e.g., tone-8s / light-16s). Then, we moved rats to a new context and extended the long-cues interval (e.g., light-32s). This caused rats to respond later to the short cue, despite never being trained to do so. Importantly, when returned to the initial training context, sham rats shifted back toward both cues original intervals. In contrast, lesion rats continued to respond at the long cues newer interval. Surprisingly, they still showed contextual modulation for the short cue, responding earlier like shams. These data suggest the hippocampus only mediates context-based timing if a cue is explicitly paired and/or rewarded across distinct contexts. Furthermore, as lesions did not impact timing measures at baseline or acquisiton for the long cues new interval, our data suggests that the hippocampus only modulates timing when context is relevant.

neuroscience↗

bioRxiv2021

Communication between the mediodorsal thalamus and prelimbic cortex regulates timing performance in rats

Predicting when future events will occur and adjusting behavior accordingly is critical to adaptive behavior. Despite this, little is known about the brain networks that encode time and how this ultimately impacts decision-making. One established finding is that the prefrontal cortex (PFC) and its non-human analogues (e.g., the rodent prelimbic cortex; PL) mediate timing. This provides a starting point for exploring the networks that support temporal processing by identifying areas that interact with the PFC during timing tasks. For example, substantial work has explored the role of frontostriatal circuits in timing. However, other areas are undoubtedly involved. The mediodorsal nucleus of the thalamus (MD) is an excellent candidate region. It shares dense, reciprocal connections with PFC-areas in both humans and non-human species and is implicated in cognition. However, causal data implicating MD-PFC interactions in cognition broadly is still sparse, and their role in timing specifically is currently unknown. To address this, we trained male rats on a time-based, decision-making task referred to as the peak-inter- val procedure. During the task, presentation of a cue instructed the rats to respond after a specific interval of time elapsed (e.g., tone-8 seconds). We incorporated two cues; each requiring a response after a distinct time-interval (e.g., tone-8 seconds / light-16 seconds). We tested the effects of either reversibly inactivating the MD or PL individually or functionally disconnecting them on performance. All manipulations caused a comparable timing deficit. Specifically, responses showed little organization in time, as if primarily guided by motivational systems. These data expand our understanding of the networks that support timing and suggest that MD-PL interactions specifically are a core component. More broadly, our results suggest that timing tasks provide a reliable assay for characterizing the role of MD-PL interactions in cognition using rodents, which has been difficult to establish in the past.

neuroscience↗