Biology subjects

O'Dell, T. J.

Publications and source records attributed to O'Dell, T. J..

6 recordsLinked to original sources

bioRxiv2026

A novel, complex-spike burst-dependent form of BCM-like metaplasticity regulates the induction of behavioral timescale synaptic plasticity

The induction of Hebbian LTP can produce a persistent, heterosynaptic suppression of LTP induction at other synapses. This form of metaplasticity, originally formalized in the Bienenstock, Cooper, and Munro (BCM) plasticity rule, generates competitive interactions between synapses and is thought to support sparse information encoding during memory formation. Importantly, although a non-Hebbian, burst-dependent form of synaptic plasticity known as behavioral timescale plasticity (BTSP) is essential for hippocampal memory encoding, little is known about the role of metaplasticity in BTSP. Thus, I examined whether the induction of BTSP at one set of synapses in the CA1 region of mouse hippocampal slices alters plasticity at other synapses. I find that the induction of BTSP by EPSP-evoked complex-spike (CS) bursts triggers a robust, but transient, heterosynaptic depression of excitatory synaptic transmission. This depression is induced by postsynaptic CS bursts, requires activation of L-type Ca2+ channels, and is mediated by activation of A1-type adenosine receptors. Notably, the heterosynaptic depression triggered by the induction of BTSP generates a CS burst-dependent form of BCM-like metaplasticity that transiently suppresses the induction of BTSP at other synapses. Together, these results provide experimental support for computational predictions that burst-dependent forms of plasticity are constrained by a distinct, burst-dependent form of BCM metaplasticity, and identify a mechanism that may contribute to sparse memory encoding during BTSP induction.

neuroscience↗

bioRxiv2026

NMDA receptor-dependent Hebbian plasticity refines hippocampal spatial representations during two-dimensional navigation learning

Hippocampal place cell activity represents an animals location in space; yet, how hippocampal neuronal population dynamics change with spatial learning and the mechanisms underlying these activity changes, which drive allocentric navigation to a learned goal, are poorly understood. To address these questions, we performed calcium imaging with a novel wire-free waterproof miniaturized microscope to image the activity of large populations of hippocampal CA1 neurons during spatial learning of a two-dimensional navigational task, the Morris water maze. We followed the same cells during learning and were able to directly examine how each neuron in the ensemble, and the ensemble as a whole, changes its response properties. We found that neuronal spatial selectivity increased and population decoding of spatial location improved as mice learned to navigate to the goal. Viral CRISPR knock out of Grin1 (encoding the essential GluN1 NMDA receptor subunit) in dorsal hippocampal neurons, dramatically reduced long-term potentiation in CA1. This manipulation also prevented the increase in spatial selectivity and improvement of population decoding with spatial learning and resulted in learning deficits in the Morris water maze. Together, our results show that dorsal hippocampus NMDAR-dependent synaptic plasticity is essential for the learning-dependent refinement of CA1 place selectivity and improvement in population decoding of space.

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bioRxiv2025

β-adrenergic receptor activation modulates the induction of complex spike burst-dependent LTP by regulating multiple forms of heterosynaptic plasticity

The modulatory neurotransmitter norepinephrine and activation of {beta}-adrenergic receptors ({beta}-ARs) has a crucial role in hippocampus-dependent forms of learning. Although {beta}-AR activation also facilitates the induction of Hebbian LTP at excitatory synapses in the hippocampus, recent findings indicate that a non-Hebbian form of synaptic plasticity, known as behavioral timescale synaptic plasticity (BTSP), underlies hippocampus-dependent spatial learning. Because little is known about the role of noradrenergic signaling in BTSP, I examined the effects of the {beta}-AR activation on a BTSP-like, complex spike (CS) burst-dependent form of LTP induced by theta-pulse stimulation (TPS) protocols in the CA1 region of mouse hippocampal slices. I find that {beta}-AR activation not only enhances the homosynaptic potentiation of synaptic transmission induced by TPS but also regulates how synapses interact during the induction of CS burst-dependent LTP. The ability of synapses to interact in a cooperative fashion to undergo CS burst-dependent LTP, which is mediated by a heterosynaptic facilitation of EPSP-evoked CS bursting induced by brief trains of TPS, was enhanced by {beta}-AR activation. Moreover, unlike conventional Hebbian LTP, where cooperative LTP induction requires near synchronous coactivation of synapses, {beta}-AR activation enabled the induction of CS burst-dependent LTP by cooperative interactions between synapses activated up to ten seconds apart. {beta}-AR activation also enhanced a potent form of synaptic competition that emerges during longer trains of TPS. This effect of {beta}-AR activation is mediated by a CS burst-dependent form of heterosynaptic depression and produces an unusual, bidirectional modulation of LTP induction where the {beta}-AR-mediated facilitation of homosynaptic LTP induction produces a heterosynaptic suppression of LTP induction at other synapses. Together, these findings indicate that {beta}-AR activation regulates fundamental properties of postsynaptic burst-dependent plasticity rules by modulating multiple forms of heterosynaptic plasticity.

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bioRxiv2021

A brain atlas of synapse protein lifetime across the mouse lifespan.

Protein turnover is required for synapse maintenance and remodelling and may impact memory duration. We quantified the lifetime of postsynaptic protein PSD95 in individual excitatory synapses across the mouse brain and lifespan, generating the Protein Lifetime Synaptome Atlas. Excitatory synapses have a wide range of protein lifetimes that may extend from a few hours to several months, with distinct spatial distributions in dendrites, neuron types and brain regions. Short protein lifetime (SPL) synapses are enriched in developing animals and in regions controlling innate behaviors, whereas long protein lifetime (LPL) synapses accumulate during development, are enriched in the cortex and CA1 where memories are stored, and are preferentially preserved in old age. The protein lifetime synaptome architecture is disrupted in an autism model, with synapse protein lifetime increased throughout the brain. These findings add a further layer to synapse diversity in the brain and enrich prevailing concepts in behavior, development, ageing and brain repair.

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bioRxiv2019

Anterior cingulate cortex activity regulates effort-based decision making

The anterior cingulate cortex (ACC) is implicated in effort exertion and choices based on effort cost, but it is still unclear how it mediates this cost-benefit evaluation. Here, male rats were trained to exert effort for a high-value reward (sucrose pellets) in a progressive ratio lever pressing task. Trained rats were then tested in two conditions: a no-choice condition where lever pressing for sucrose was the only available food option, and a choice condition where a low-value reward (lab chow) was freely available as an alternative to pressing for sucrose. Disruption of ACC--via either chemogenetic inhibition or excitation--reduced lever pressing in the choice, but not in the no-choice, condition. We next looked for value coding cells in ACC during effortful behavior and reward consumption phases during choice and no-choice conditions. For this, we utilized in vivo miniaturized fluorescence microscopy to reliably track responses of the same cells and compare how ACC neurons respond during the same effortful behavior where there was a choice versus when there was no-choice. We found that lever-press and sucrose-evoked responses were significantly weaker during choice compared to no-choice sessions, which may have rendered them more susceptible to chemogenetic disruption. Taken together, findings from our interference experiments and neural recordings suggest that a mechanism by which ACC mediates effortful decisions is in the discrimination of the utility of available options. ACC regulates these choices by providing a stable population code for the relative value of different options. Significance StatementThe anterior cingulate cortex (ACC) is implicated in effort-based decision making. Here, we used chemogenetics and in vivo calcium imaging to explore its mechanism. Rats were trained to lever press for a high-value reward and tested in two conditions: a no-choice condition where lever pressing for the high-value reward was the only option, and a choice condition where a low-value reward was also available. Inhibition or excitation of ACC reduced effort toward the high value option, but only in the choice condition. Neural responses in ACC were weaker in the choice compared to the no-choice condition. A mechanism by which ACC regulates effortful decisions is in providing a stable population code for the discrimination of the utility of available options.

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bioRxiv2019

Dissociable roles for Anterior Cingulate Cortex and Basolateral Amygdala in Decision Confidence and Learning under Uncertainty

It has been suggested the subjective sense of certainty, or confidence, in ambiguous sensory cues can alter the interpretation of reward feedback and facilitate learning. We trained rats to report the orientation of ambiguous visual stimuli according to a spatial stimulus-response rule. Following choice, rats could wait a self-timed delay for reward or initiate a new trial. Waiting times increased with discrimination accuracy, demonstrating that this measure could be used as a proxy for confidence. Chemogenetic silencing of BLA shortened waiting times overall whereas ACC inhibition rendered waiting times insensitive to confidence-modulating attributes of visual stimuli, suggesting contribution of ACC but not BLA to confidence computations. Subsequent reversal learning was enhanced by confidence. Both ACC and BLA inhibition blocked this enhancement but via differential modulation of learning strategies and consistency in using learned rules. Altogether, we demonstrate dissociable roles for ACC and BLA in transmitting confidence and learning under uncertainty.

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