Publications by authors named "Mary H Patton"

Synaptic plasticities, such as long-term potentiation (LTP) and depression (LTD), tune synaptic efficacy and are essential for learning and memory. Current studies of synaptic plasticity in humans are limited by a lack of adequate human models. Here, we modeled the thalamocortical system by fusing human induced pluripotent stem cell-derived thalamic and cortical organoids.

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Synaptic plasticities, such as long-term potentiation (LTP) and depression (LTD), tune synaptic efficacy and are essential for learning and memory. Current studies of synaptic plasticity in humans are limited by a lack of adequate human models. Here, we modeled the thalamocortical system by fusing human induced pluripotent stem cell-derived thalamic and cortical organoids.

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Impulsive choice has enduring trait-like characteristics and is defined by preference for small immediate rewards over larger delayed ones. Importantly, it is a determining factor in the development and persistence of substance use disorder (SUD). Emerging evidence from human and animal studies suggests frontal cortical regions exert influence over striatal reward processing areas during decision-making in impulsive choice or delay discounting (DD) tasks.

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Recent proteome and transcriptome profiling of Alzheimer's disease (AD) brains reveals RNA splicing dysfunction and U1 small nuclear ribonucleoprotein (snRNP) pathology containing U1-70K and its N-terminal 40-KDa fragment (N40K). Here we present a causative role of U1 snRNP dysfunction to neurodegeneration in primary neurons and transgenic mice (N40K-Tg), in which N40K expression exerts a dominant-negative effect to downregulate full-length U1-70K. N40K-Tg recapitulates N40K insolubility, erroneous splicing events, neuronal degeneration and cognitive impairment.

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Article Synopsis
  • Williams-Beuren syndrome (WBS) is a rare genetic disorder caused by the deletion of about 27 genes, leading to cognitive deficits but enhanced musical and auditory abilities.
  • Mouse models of WBS show improved frequency discrimination in their auditory cortex due to hyperexcitable interneurons.
  • The gene Gtf2ird1 is linked to WBS effects by regulating the neuropeptide receptor VIPR1, which influences auditory processing, suggesting a specific genetic mechanism behind enhanced auditory skills in individuals with WBS.
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Inhibitory fast-spiking interneurons in the dorsal striatum regulate actions and action strategies, including habits. Fast-spiking interneurons are widely believed to synchronize their firing due to the electrical synapses formed between these neurons. However, neuronal modelling data suggest convergent cortical input may also drive synchrony in fast-spiking interneuron networks.

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Schizophrenia is a severe, chronic psychiatric disorder that devastates the lives of millions of people worldwide. The disease is characterized by a constellation of symptoms, ranging from cognitive deficits, to social withdrawal, to hallucinations. Despite decades of research, our understanding of the neurobiology of the disease, specifically the neural circuits underlying schizophrenia symptoms, is still in the early stages.

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Article Synopsis
  • Striatal fast-spiking interneurons (FSIs) strongly inhibit striatal output neurons and play a critical role in action learning through the coordination of their activity.
  • Researchers used in vivo calcium imaging and machine learning to study FSIs in mice, investigating how their activity relates to movement.
  • The findings indicated that FSIs collectively encode the speed of different action components like walking and head movements, supporting the idea that their dynamics contribute to a model of ensemble inhibition in guiding actions.
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  • The nucleus accumbens is crucial for processing rewards and is mainly made up of medium spiny neurons, where the balance of excitation and inhibition influences its output.
  • Research reveals that long-term depression of inhibitory synaptic transmission occurs in this area, which is less understood than excitatory synaptic plasticity.
  • The study highlights that this long-term depression is mediated by TrkB receptors and enhanced by ethanol, suggesting that this mechanism could play a role in how ethanol affects reward processing in the brain.
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  • The study investigates how glutamatergic projections from the thalamic rostral intralaminar nuclei (rILN) influence dopamine (DA) release and reward-seeking behavior in the dorsal striatum (DS).
  • It reveals that activating rILN inputs triggers burst-firing in cholinergic interneurons, affecting D2 receptor activities, which in turn modulates DA-related signaling.
  • The research suggests that rILN activation enhances the pursuit of rewards by stimulating striatal cholinergic interneurons, thereby adding complexity to our understanding of how DA release operates in the brain.
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Decades of work in Aplysia californica established the general rule that principles of synaptic plasticity and their molecular mechanisms are evolutionarily conserved from mollusks to mammals. However, an exquisitely sensitive, activity-dependent homosynaptic mechanism that protects against the depression of neurotransmitter release in Aplysia sensory neuron terminals has, to date, not been uncovered in other animals, including mammals. Here, we discover that depression at a mammalian synapse that is implicated in habit formation and habit learning acceleration by ethanol, the fast-spiking interneuron (FSI) to medium spiny principal projection neuron (MSN) synapse of the dorsolateral striatum, is subject to this type of synaptic protection.

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Cortical circuits are particularly sensitive to incoming sensory information during well-defined intervals of postnatal development called 'critical periods'. The critical period for cortical plasticity closes in adults, thus restricting the brain's ability to indiscriminately store new sensory information. For example, children acquire language in an exposure-based manner, whereas learning language in adulthood requires more effort and attention.

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The prevalence of nicotine dependence is higher than that for any other substance abuse disorder; still, the underlying mechanisms are not fully established. To this end, we studied acute effects by nicotine on neurotransmission in the dorsolateral striatum, a key brain region with respect to the formation of habits. Electrophysiological recordings in acutely isolated brain slices from rodent showed that nicotine (10 nm to 10 μm) produced an LTD of evoked field potentials.

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Altered brain energy homeostasis is a key adaptation occurring in the cocaine-addicted brain, but the effect of cocaine on the fundamental source of energy, mitochondria, is unknown. We demonstrate an increase of dynamin-related protein-1 (Drp1), the mitochondrial fission mediator, in nucleus accumbens (NAc) after repeated cocaine exposure and in cocaine-dependent individuals. Mdivi-1, a demonstrated fission inhibitor, blunts cocaine seeking and locomotor sensitization, while blocking c-Fos induction and excitatory input onto dopamine receptor-1 (D1) containing NAc medium spiny neurons (MSNs).

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The dorsolateral striatum mediates habit formation, which is expedited by exposure to alcohol. Across species, alcohol exposure disinhibits the DLS by dampening GABAergic transmission onto this structure's principal medium spiny projection neurons (MSNs), providing a potential mechanistic basis for habitual alcohol drinking. However, the molecular and circuit components underlying this disinhibition remain unknown.

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The ventral tegmental area (VTA) has been implicated in a number of psychiatric disorders, including schizophrenia, depression, and bipolar disorder. One major regulator of the mesolimbic dopaminergic system is the medial prefrontal cortex (mPFC), which makes direct and indirect connections to the hippocampus and amygdala, as well as directly to the VTA. The mPFC is comprised of two subregions: the infralimbic and prelimbic cortices (ilPFC and plPFC).

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Schizophrenia is characterized by alterations in cortico-limbic processes believed to involve modifications in activity within the prefrontal cortex (PFC) and the hippocampus. The nucleus accumbens (NAc) integrates information from these 2 brain regions and is involved in cognitive and psychomotor functions that are disrupted in schizophrenia, indicating an important role for this structure in the pathophysiology of this disorder. In this study, we used in vivo electrophysiological recordings from the NAc and the PFC of adult rats and the MAM developmental disruption rodent model of schizophrenia to explore the influence of the medial PFC on the hippocampal-accumbens pathway.

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The nucleus accumbens (NAc) receives converging inputs from the medial prefrontal cortex (mPFC) and the hippocampus which have competitive interactions in the NAc to influence motivational drive. We have previously shown altered synaptic plasticity in the hippocampal-NAc pathway in the methylazoxymethanol acetate (MAM) developmental model of schizophrenia in rodents that is dependent on cortical inputs. Thus, because mPFC-hippocampal balance is known to be partially altered in this model, we investigated potential pathological changes in the hippocampal influence over cortex-driven NAc spike activity.

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