Biology subjects

Logan, C. N.

Publications and source records attributed to Logan, C. N..

4 recordsLinked to original sources

bioRxiv2026

An Operant-based Touchscreen Morph Discrimination Task Does Not Detect Age-related Mnemonic Similarity Deficits in Rats

The Mnemonic Similarity Task (MST) is highly sensitive to age-related cognitive decline in humans and has been adapted for rodents using 3D objects, where aged animals show deficits in discriminating similar lures. To improve translational alignment with human testing and increase automation, we developed a touchscreen-based rat analog using a morphed Object-Cued Spatial Choice (OCSC) task with 2D image stimuli. Young (4-month) and aged (21-month) male and female Fischer 344 x Brown Norway hybrid rats were trained in Bussey-Saksida touchscreen chambers and tested on discrimination performance using image pairs that varied parametrically in feature overlap. We also assessed perirhinal cortical engagement in a subset of animals using Arc expression as a readout of activity-related principal cell firing following low-and high-overlap task epochs. Across shaping and procedural training, aged rats required more errors to reach criterion on one stimulus set, but both age groups successfully acquired the task. During morph testing, performance declined systematically as stimulus similarity increased, confirming that the task manipulated discrimination difficulty. However, contrary to expectations, young and aged rats performed similarly across overlap conditions, with no significant age-related impairment. In the Arc experiment, discrimination accuracy was again reduced by greater stimulus overlap, but Arc expression in perirhinal cortex did not differ reliably by age or overlap condition, although expression was associated with behavioral accuracy and deep layers showed higher ensemble similarity than superficial layers. These findings indicate that, while the touchscreen morph OCSC task is sensitive to stimulus similarity, it does not detect the robust age-related mnemonic discrimination deficits previously observed with 3D object-based rodent MST paradigms, underscoring the importance of considering ethological relevance when designing translational cognitive assays.

neuroscience↗

bioRxiv2022

Unilateral Perforant Path Transection Does Not Alter Lateral Entorhinal Cortical or Hippocampal CA3 Arc Expression

It is well established that degradation of perforant path fibers is associated with age-related cognitive dysfunction and CA3 hyperactivity. Whether this fiber loss triggers a cascade of other functional changes within the hippocampus circuit has not been causatively established, however. Thus, the current study evaluated the effect of perforant path fiber loss on neuronal activity in CA3 and layer II of the lateral entorhinal cortex (LEC) in relation to mnemonic similarity task performance. Expression of the immediate early gene Arc was quantified in rats that received a unilateral right hemisphere transection of the perforant path or sham surgery that cut the cortex but left the fibers intact. Behavior-related expression of Arc mRNA was measured to test the hypothesis that fiber loss leads to elevated activation of CA3 and LEC neurons, as previously observed in aged rats that were impaired on the mnemonic similarity task. Transection of perforant path fibers, which has previously been shown to lead to a decline in mnemonic similarity task performance, did not alter Arc expression. Arc expression in CA3, however, was correlated with task performance on the more difficult discrimination trials across both surgical groups. These observations further support a link between CA3 activity and mnemonic similarity task performance but suggest the reduced input from the entorhinal cortex to the hippocampus, as observed in old age, does not causatively elevate CA3 activity.

neuroscience↗

bioRxiv2020

Ceftriaxone and mGlu2/3 interactions in the nucleus accumbens core affect the reinstatement of cocaine-seeking in male and female rats

RationaleThe beta-lactam antibiotic ceftriaxone reliably attenuates the reinstatement of cocaine-seeking. While the restoration of nucleus accumbens core (NA core) GLT-1 expression is necessary for ceftriaxone to attenuate reinstatement, AAV-mediated GLT-1 overexpression is not sufficient to attenuate reinstatement and does not prevent glutamate efflux during reinstatement. AimsHere, we test the hypothesis that ceftriaxone attenuates reinstatement through interactions with glutamate autoreceptors mGlu2 and mGlu3 in the NA core. MethodsMale and female rats self-administered cocaine for 12 days followed by 2-3 weeks of extinction training. During the last 6-10 days of extinction, rats received ceftriaxone (200 mg/kg IP) or vehicle. In experiment 1, rats were killed, and NA core tissue was biotinylated for assessment of total and surface expression of mGlu2 and mGlu3 via western blotting. In experiment 2, we tested the hypothesis that mGlu2/3 signaling is necessary for ceftriaxone to attenuate cue- and cocaine-primed reinstatement by administering bilateral intra-NA core infusion of mGlu2/3 antagonist LY341495 or vehicle immediately prior to reinstatement testing. ResultsmGlu2 expression was reduced by cocaine and restored by ceftriaxone. There were no effects of cocaine or ceftriaxone on mGlu3 expression. We observed no effects of estrus on expression of either protein. The antagonism of mGlu2/3 in the NA core during both cue- and cocaine-primed reinstatement tests prevented ceftriaxone from attenuating reinstatement. ConclusionsThese results indicate that ceftriaxones effects depend on mGlu2/3 function and possibly mGlu2 receptor expression. Future work will test this hypothesis by manipulating mGlu2 expression in pathways that project to the NA core.

neuroscience↗

bioRxiv2020

Role of prefrontal cortex projections to the nucleus accumbens core in mediating the effects of ceftriaxone on cued cocaine relapse

Ceftriaxone is an antibiotic that reliably attenuates the reinstatement of cocaine-seeking after extinction while preventing the nucleus accumbens (NA) core glutamate efflux that drives reinstatement. However, when rats undergo abstinence without extinction, ceftriaxone attenuates context-primed relapse but NA core glutamate efflux still increases. Here we sought to determine if the same would occur when relapse is prompted by both context and discrete cues (context+cues) after cocaine abstinence. Male rats self-administered intravenous cocaine for 2 hr/day for 2 weeks. Cocaine delivery was accompanied by drug-associated cues (light+tone). Rats were then placed into abstinence with daily handling but no extinction training for two weeks. Ceftriaxone (200 mg/kg IP) or vehicle was administered during the last 6 days of abstinence. During a context+cue relapse test, microdialysis procedures were conducted. Rats were perfused at the end of the test for later Fos analysis. A separate cohort of rats was infused with the retrograde tracer cholera toxin B in the NA core and underwent the same self-administration and relapse procedures. Ceftriaxone increased baseline glutamate and attenuated both context+cue-primed relapse and NA core glutamate efflux during this test. Ceftriaxone reduced Fos expression in regions sending projections to the NA core (prefrontal cortex, basolateral amygdala, ventral tegmental area) and specifically reduced Fos in prelimbic cortex and not infralimbic cortex neurons projecting to the NA core. Thus, when relapse is primed by drug-associated cues and context, ceftriaxone is able to attenuate relapse by preventing NA core glutamate efflux, likely through reducing activity in prelimbic NA core-projecting neurons.

neuroscience↗