Synaptic Effects Induced by Alcohol

Lovinger, David M.; Roberto, Marisa

doi:10.1007/7854_2022_412

Cited by 8 publications

(9 citation statements)

References 618 publications

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“…Moreover, we found increased frequency and amplitude of asynchronous IPSCs at DLS-SNr synapses indicating an increased strength of DLS-SNr inputs. Our findings imply the presence of a postsynaptic mechanism which potentiates DLS-SNr inputs via an increased number of GABAergic synapses, an increased availability of GABAA receptors, or changes in channel conductance due to modifications in their subunit composition 3,4 . In parallel, compensatory presynaptic changes might explain the increase in PPR at DLS-SNr inputs, including altered GPCR signaling.…”

Section: Differential Synaptic Organization Of Inputs To the Medial A...mentioning

confidence: 77%

Chronic alcohol induces subcircuit-specific striatonigral plasticity shifting action control to the sensorimotor striatum

Sitzia,

Bariselli,

Gracias

et al. 2023

Preprint

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While cortico-striatal circuit deficits contribute to Alcohol Use Disorder, the impact of alcohol on synaptic function in the basal ganglia output, the substantia nigra pars reticulata (SNr), remains unclear. Here, we found that the inputs from the dorsomedial (DMS) and dorsolateral striatum (DLS) differ in their presynaptic properties and target molecularly distinct subpopulations of SNr neurons. We also discovered that indirect pathway subthalamic (STN) inputs to the medial and lateral SNr have different presynaptic properties and that STN inputs are stronger in the lateral SNr. Chronic alcohol exposure (CIE) potentiated DLS inputs but did not affect the strength and presynaptic release properties of DMS and subthalamic inputs to SNr neurons. Chemogenetic inhibition of DLS direct pathway projection neurons impaired action performance in an operant conditioning task in CIE mice but not control mice. Overall, our work identifies a synaptic mechanism whereby chronic alcohol induces a gain of function for action control in direct pathway neurons in the dorsolateral striatum.TeaserChronic alcohol selectively potentiates DLS synaptic inputs to the SNr, enhancing their role in action control.

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Section: Differential Synaptic Organization Of Inputs To the Medial A...mentioning

confidence: 77%

Chronic alcohol induces subcircuit-specific striatonigral plasticity shifting action control to the sensorimotor striatum

Sitzia,

Bariselli,

Gracias

et al. 2023

Preprint

Self Cite

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“…Although the literature is highly variable and sometimes contradictory, it is important to note that much of this heterogeneity is likely due to distinct experimental conditions, in particular to the regimes of alcohol exposure. Overall, however, the evidence converges on at least two observations, first, at the circuit level there is a shift in the cellular excitation/inhibition balance towards more excitable states [ 76 , 81 ] and, second, an initial impairment in synaptic plasticity resolves soon after alcohol withdrawal [ 82 ]. Our findings in PD rats fit well with these observations.…”

Section: Discussionmentioning

confidence: 87%

Alcohol-induced damage to the fimbria/fornix reduces hippocampal-prefrontal cortex connection during early abstinence

Pérez-Cervera,

De Santis,

Marcos

et al. 2023

acta neuropathol commun

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Introduction Alcohol dependence is characterized by a gradual reduction in cognitive control and inflexibility to contingency changes. The neuroadaptations underlying this aberrant behavior are poorly understood. Using an animal model of alcohol use disorders (AUD) and complementing diffusion-weighted (dw)-MRI with quantitative immunohistochemistry and electrophysiological recordings, we provide causal evidence that chronic intermittent alcohol exposure affects the microstructural integrity of the fimbria/fornix, decreasing myelin basic protein content, and reducing the effective communication from the hippocampus (HC) to the prefrontal cortex (PFC). Using a simple quantitative neural network model, we show how disturbed HC-PFC communication may impede the extinction of maladaptive memories, decreasing flexibility. Finally, combining dw-MRI and psychometric data in AUD patients, we discovered an association between the magnitude of microstructural alteration in the fimbria/fornix and the reduction in cognitive flexibility. Overall, these findings highlight the vulnerability of the fimbria/fornix microstructure in AUD and its potential contribution to alcohol pathophysiology. Summary Fimbria vulnerability to alcohol underlies hippocampal-prefrontal cortex dysfunction and correlates with cognitive impairment.

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“…Acetaldehyde is a highly reactive molecule and is oxidized to acetate by mitochondrial acetaldehyde dehydrogenase (ALDH2) resulting in generation of NADH. Since alcohol can easily cross the BBB, it has been shown to directly affect numerous molecular targets in the brain, including synaptic function and transmission (Lovinger & Roberto, 2013). Moreover, in the brain, it has been shown that alcohol can suppress glucose metabolism, and therefore, acetate can be used as an energy source (Tanabe et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

Excessive intragastric alcohol administration exacerbates hepatic encephalopathy and provokes neuronal cell death in male rats with chronic liver disease

Tamnanloo,

Chen,

Oliveira

et al. 2024

J of Neuroscience Research

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Hepatic encephalopathy (HE) is defined as decline in neurological function during chronic liver disease (CLD). Alcohol is a major etiological factor in the pathogenesis of fibrosis/cirrhosis and has also been documented to directly impact the brain. However, the role of alcohol in the development of HE in CLD remains unclear. Here, we investigated the impact of excessive alcohol administration on neurological deterioration in rats with CLD. Starting day 7 post‐BDL surgery, rats were administered alcohol twice daily (51% v/v ethanol, 3 g/kg, via gavage) for 4 weeks. Motor coordination was assessed weekly using rotarod and anxiety‐like behavior was evaluated with open field and elevated plus maze at 5 weeks. Upon sacrifice, brains were collected for western blot and immunohistochemical analyses to investigate neuronal integrity and oxidative stress status. Alcohol worsened motor coordination performance and increased anxiety‐like behavior in BDL rats. Impairments were associated with decreased neuronal markers of NeuN and SMI311, increased apoptotic markers of cleaved/pro‐caspase‐3 and Bax/Bcl2, increased necroptosis markers of pRIP3 and pMLKL, decreased total antioxidant capacity (TAC), and increased 4‐hydroxynonenal (4‐HNE)modified proteins in the cerebellum of BDL‐alcohol rats when compared to respective controls. Immunofluorescence confirmed the colocalization of cleaved caspase‐3 and pMLKL in the granular neurons of the cerebellum of BDL‐alcohol rats. Excessive alcohol consumption exacerbates HE which leads to associated apoptotic and necroptotic neuronal loss in the cerebellum of BDL‐alcohol rats. Additionally, higher levels of 4‐HNE and decreased TAC in the cerebellum of BDL‐alcohol rats suggest oxidative stress is the triggering factor of apoptotic and necroptotic neuronal loss/injury.

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Synaptic Effects Induced by Alcohol

Cited by 8 publications

References 618 publications

Chronic alcohol induces subcircuit-specific striatonigral plasticity shifting action control to the sensorimotor striatum

Chronic alcohol induces subcircuit-specific striatonigral plasticity shifting action control to the sensorimotor striatum

Alcohol-induced damage to the fimbria/fornix reduces hippocampal-prefrontal cortex connection during early abstinence

Excessive intragastric alcohol administration exacerbates hepatic encephalopathy and provokes neuronal cell death in male rats with chronic liver disease

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