Biomedical subjects

Craig Weiss

Publications and source records attributed to Craig Weiss.

8 recordsLinked to original sources

PubMed2026

Individual Differences in Cognitive Aging Rodent Datasets (ID-CARD): A collaborative platform for behavioral analysis across the lifespan.

Understanding cognitive aging requires approaches that capture individual variability while enabling integration across studies. In rodent models, behavioral data are central to this effort, yet cross-laboratory differences in experimental design limit comparability and constrain secondary analysis. To address this gap, we developed the Individual Differences in Cognitive Aging Rodent Datasets (ID-CARD), a first-of-its-kind collaborative repository aggregating trial-level Morris water maze data from multiple laboratories. ID-CARD is designed to support large-scale, integrative analyses and to facilitate secondary use of existing behavioral data in alignment with emerging data-sharing and transparency initiatives. Rather than imposing retrospective harmonization of experimental protocols, we implemented a normalization and modeling framework that enables comparison of learning trajectories while preserving meaningful variation across studies. Behavioral data from > 5000 rats spanning common strains, both sexes, and multiple ages were normalized in training and performance domains and fit with a logarithmic function to derive an error accumulation rate coefficient (EARC) as a measure of spatial learning. Age was strongly associated with increased EARC, indicating attenuated learning, even after adjusting for non-spatial cue performance. Analyses of goodness of fit revealed systematic structure in learning dynamics, where age was associated with reduced learning-curve conformity after accounting for overall performance. Inter-individual variability in spatial learning also increased with age, with strain-specific interactions. These findings demonstrate that integrated analysis of heterogeneous behavioral datasets can yield robust, individual-level insights into cognitive aging. ID-CARD provides a scalable resource and analytic framework to advance discovery in behavioral neuroscience by enabling reuse, integration, and comparative analysis of existing data.

Cognitive aging↗

PubMed2006

Vibrissa-signaled eyeblink conditioning induces somatosensory cortical plasticity.

Whisker deflection conditioned stimuli (CS) were demonstrated to activate physiologically and anatomically defined barrels in the contralateral somatosensory cortex and to support trace-eyeblink conditioned responses when paired with corneal airpuff unconditioned stimuli in rabbits. Analysis of cytochrome-oxidase-stained somatosensory whisker-associated cortical barrels revealed a row-specific expansion of the conditioned compared with the nontrained hemisphere. This expansion was not evident in pseudo-conditioned rabbits, suggesting that this expansion of conditioned cortical barrels in response to a hippocampal- and forebrain-dependent learning task (trace conditioning) is associative rather than activity dependent. Using whisker stimulation as a CS in the well studied eyeblink conditioning paradigm will facilitate characterizing sensory cortical involvement in controlling and modulating an associatively learned response at the neural systems and cellular level.

Animals↗

PubMed2005

GLYX-13: a monoclonal antibody-derived peptide that acts as an N-methyl-D-aspartate receptor modulator.

We previously created a monoclonal antibody (MAb), B6B21, that acts as a partial agonist at the glycine site of the N-methyl-d-aspartate (NMDA) receptor [Moskal, J.R., Schaffner, A.E., 1986. Monoclonal antibodies to the dentate gyrus: immunocytochemical characterization and flow cytometric analysis of hippocampal neurons bearing a unique cell-surface antigen. J. Neurosci. 6, 2045-2053.]. The hypervariable region of the light chain of B6B21 was cloned and sequenced. Peptides were then synthesized based on this sequence information and screened using rat hippocampal membrane preparations to measure [(3)H]MK-801 binding in the presence of 7-chlorokynurenic acid, a glycine site-specific competitive inhibitor of NMDA receptor [Moskal, J.R., Yamamoto, H., Colley, P.A., 2001. The use of antibody engineering to create novel drugs that target N-methyl-d-aspartate receptors. Curr. Drug Targets 2, 331-345.]. Peptides that were able to increase [(3)H]MK-801 binding in a dose-dependent manner under these conditions were named Glyxins. Here we report that GLYX-13, a tetrapeptide (TPPT-amide), was found to readily cross the blood-brain barrier and modulate the NMDA receptor in a glycine-like fashion when examined pharmacologically and electrophysiologically. When GLYX-13 was administered to rats at 0.5-1.0mg/kg i.v., a significant enhancement in learning was observed using a hippocampus-dependent trace eye blink conditioning paradigm. These data indicate that the Glyxins are a new class of NMDA receptor modulators that may have therapeutic potential. Based on the broad agonist range in vitro and the potent cognitive-enhancing properties in a valid in vivo model of learning, GLYX-13 is a new drug candidate with potential for the treatment of cognitive disorders.

Animals↗

PubMed2005

A fiber optic-based system for behavioral eyeblink measurement in a MRI environment.

We previously described a reliable system to control the timing of multiple stimuli and to detect behavioral eyeblink responses in fMRI studies of learning in animals. Here, we report a significant advancement of the original system, which incorporates a fiber-optic probe in order to avoid the interference associated with the application of pulsed field gradients during MR imaging, particularly echo planar imaging. Eyeblink responses recorded with our fiber-optic probe and modified detection circuit demonstrate the ability of our new system to acquire behavioral data free of gradient-induced artifacts, thereby eliminating the need for low-pass filtering. This fiber optic-based system should be applicable to both animal and human imaging experiments.

Animals↗

PubMed2003

fMRI of the conscious rabbit during unilateral classical eyeblink conditioning reveals bilateral cerebellar activation.

The relative contributions of the ipsilateral and contralateral cerebellar cortex and deep nuclei to delay eyeblink conditioning have been debated and are difficult to survey entirely using typical electrophysiological and lesion techniques. To address these issues, we used single-event functional magnetic resonance imaging (fMRI) in the conscious rabbit to visualize the entire cerebellum simultaneously during eyeblink conditioning sessions. Examination of the blood oxygenation level-dependent (BOLD) response to a visual conditioning stimulus early in training revealed significant bilateral learning-related increases in the BOLD response in the anterior interpositus nucleus (IPA) and significant bilateral deactivation in hemispheric lobule VI (HVI) of the cerebellar cortex. Later in training, the BOLD response remained bilateral in the cortex and predominantly ipsilateral in the IPA. Conditioning stimulus-alone trials after conditioning revealed that both sides of HVI were affected similarly but that only the ipsilateral interpositus nucleus was activated. These results suggest that both sides of HVI normally influence the side of the IPA being conditioned and illustrate how fMRI can be used to examine multiple brain regions simultaneously in an awake, behaving animal to discover more rapidly the neural substrates of learning and memory.

Animals↗

PubMed2003

Functional magnetic resonance imaging in the awake rabbit: a system for stimulus presentation and response detection during eyeblink conditioning.

We describe a reliable system to control the timing of multiple stimuli and to detect eyeblink responses during functional magnetic resonance imaging (fMRI). The methods for stimulus delivery and timing, eyeblink detection, and response quantification are described in detail. We are using these methods in awake rabbits to study eyeblink conditioning (EBC) as a model paradigm for the study of learning and memory. Examples of conditioned eyeblinks in the awake rabbit during fMRI are presented for validation of our techniques. The results indicate that eyeblinks can be reliably recorded during fMRI, and that neither the stimulus delivery nor the response detection interferes with each other or affect the quality of the images. The combined fMRI/behavioral techniques should be useful for examining the entire brain simultaneously during the associative learning of a conditioned reflex in an animal model system.

Animals↗

PubMed2003

Activity profiles of single neurons in caudal anterior cingulate cortex during trace eyeblink conditioning in the rabbit.

Acquisition of trace eyeblink conditioning involves the association of a conditioned stimulus (CS) with an unconditioned stimulus (US) separated by a stimulus-free trace interval. This form of conditioning is dependent upon the hippocampus and the caudal anterior cingulate cortex (AC), in addition to brain stem and cerebellar circuitry. Hippocampal involvement in trace eyeblink conditioning has been studied extensively, but the involvement of caudal AC is less well understood. In the present study, we compared neuronal responses from rabbits given either paired (trace conditioning) or unpaired (pseudoconditioning) presentations of the CS and US. Presentation of the CS elicited significant increases in neuronal activity at the onset of both trace conditioning and pseudoconditioning. A robust CS-elicited neuronal response persisted throughout the first 2 days of trace conditioning, declining gradually across subsequent training sessions. In contrast, the magnitude of the CS-elicited excitatory response during pseudoconditioning began to decline within the first 10 trials. Neurons exhibiting excitatory responses to the CS during trace conditioning also exhibited excitatory responses to the US that were significantly greater in magnitude than US-elicited responses during pseudoconditioning. CS-elicited decreases in neuronal activity became more robust over the course of trace conditioning compared to pseudoconditioning. Reductions in activity during the CS interval consistently preceded excitation in both training groups, suggesting that the CS-elicited decreases in neuronal activity may serve to increase the signal-to-noise ratio of the excitatory response to the tone. Taken together, these data suggest that the caudal AC is involved early in trace eyeblink conditioning and that maintenance of the CS-elicited excitatory response may serve to signal the salience of the tone.

Animals↗

PubMedDate not supplied

Acute stress facilitates trace eyeblink conditioning in C57BL/6 male mice and increases the excitability of their CA1 pyramidal neurons.

The effects of stress (restraint plus tail shock) on hippocampus-dependent trace eyeblink conditioning and hippocampal excitability were examined in C57BL/6 male mice. The results indicate that the stressor significantly increased the concentration of circulating corticosterone, the amount and rate of learning relative to nonstressed conditioned mice, and the excitability of CA1 hippocampal pyramidal neurons. Behaviorally, there was no effect of the stressor on control mice that received unpaired presentations of the tone and periorbital shock, i.e., neither stressed nor nonstressed control mice showed an increase in conditioned responding that was above baseline levels. Biophysically, the stressor significantly decreased the amplitude of the post-burst afterhyperpolarization (AHP) and decreased spike frequency accommodation relative to cells from nonstressed control mice. The effect was significant for mice that were stressed either 1 h or 24 h earlier. The results suggest that the stressor increases the excitability of hippocampal pyramidal neurons and that the mechanism underlying this increase may contribute to the more rapid acquisition of hippocampally dependent eyeblink conditioning.

Action Potentials↗