Long-term, cell type-specific effects of prenatal stress on dorsal striatum and relevant behaviors in mice.

Maternal stress during pregnancy, or prenatal stress, is a risk factor for neurodevelopmental disorders in offspring, including autism spectrum disorder (ASD). In ASD, dorsal striatum displays abnormalities correlating with symptom severity, but there is a gap in knowledge about dorsal striatal cellular and molecular mechanisms that may contribute. Using a mouse model, we investigated how prenatal stress impacted striatal-dependent behavior in adult offspring.

Sustained behaviour: Encoding of cumulative experience in the anterior cingulate.

Time is a ubiquitous dimension of behaviour. A new study demonstrates that low-dimensional temporal drift in rodent anterior cingulate ensembles encodes cumulative experience. These data provide fresh insight into how neurons encode extended periods of time to guide high-level behaviours.

Regulator of G protein signaling 6 (RGS6) in dopamine neurons promotes EtOH seeking, behavioral reward, and susceptibility to relapse.

Mesolimbic dopamine (DA) transmission is believed to play a critical role in mediating reward responses to drugs of abuse, including alcohol (EtOH). The neurobiological mechanisms underlying EtOH-seeking behavior and dependence are not fully understood, and abstinence remains the only effective way to prevent alcohol use disorders (AUDs). Here, we developed novel RGS6; DAT-iCreER mice to determine the role of RGS6 in DA neurons on EtOH consumption, reward, and relapse behaviors.

Sex similarities and dopaminergic differences in interval timing.

Rodent behavioral studies have largely focused on male animals, which has limited the generalizability and conclusions of neuroscience research. Working with humans and rodents, we studied sex effects during interval timing that requires participants to estimate an interval of several seconds by making motor responses. Interval timing requires attention to the passage of time and working memory for temporal rules.

Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures.

Background: Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by diffuse spread of alpha-synuclein (α-syn) throughout the brain. Patients with PDD and DLB have a neuropsychological pattern of deficits that include executive dysfunction, such as abnormalities in planning, timing, working memory, and behavioral flexibility. The prefrontal cortex (PFC) plays a major role in normal executive function and often develops α-syn aggregates in DLB and PDD.

Regulator of G protein signaling 6 (RGS6) in ventral tegmental area (VTA) dopamine neurons promotes EtOH seeking, behavioral reward and susceptibility to relapse.

Mesolimbic dopamine (DA) transmission is believed to play a critical role in mediating reward responses to drugs of abuse, including alcohol (EtOH). EtOH is the most abused substance worldwide with chronic consumption often leading to the development of dependence and abuse. Unfortunately, the neurobiological mechanisms underlying EtOH-seeking behavior and dependence are not fully understood, and abstinence remains the only effective way to prevent alcohol use disorders (AUDs).

Complementary cognitive roles for D2-MSNs and D1-MSNs during interval timing.

The role of striatal pathways in cognitive processing is unclear. We studied dorsomedial striatal cognitive processing during interval timing, an elementary cognitive task that requires mice to estimate intervals of several seconds and involves working memory for temporal rules as well as attention to the passage of time. We harnessed optogenetic tagging to record from striatal D2-dopamine receptor-expressing medium spiny neurons (D2-MSNs) in the indirect pathway and from D1-dopamine receptor-expressing MSNs (D1-MSNs) in the direct pathway.

Sex similarities and dopaminergic differences in interval timing.

Rodent behavioral studies have largely focused on male animals, which has limited the generalizability and conclusions of neuroscience research. Working with humans and rodents, we studied sex effects during interval timing that requires participants to estimate an interval of several seconds by making motor responses. Interval timing requires attention to the passage of time and working memory for temporal rules.

Glycolysis-enhancing α-adrenergic antagonists modify cognitive symptoms related to Parkinson's disease.

Terazosin is an α-adrenergic receptor antagonist that enhances glycolysis and increases cellular ATP by binding to the enzyme phosphoglycerate kinase 1 (PGK1). Recent work has shown that terazosin is protective against motor dysfunction in rodent models of Parkinson's disease (PD) and is associated with slowed motor symptom progression in PD patients. However, PD is also characterized by profound cognitive symptoms.

Alpha-synuclein pre-formed fibrils injected into prefrontal cortex primarily spread to cortical and subcortical structures and lead to isolated behavioral symptoms.

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by diffuse spread of alpha-synuclein (α-syn) throughout the brain. Patients with PDD and DLB have a neuropsychological pattern of deficits that include executive dysfunction, such as abnormalities in planning, timing, working memory, and behavioral flexibility. The prefrontal cortex (PFC) plays a major role in normal executive function and often develops α-syn aggregates in DLB and PDD.

Mice expressing P301S mutant human tau have deficits in interval timing.

Interval timing is a key executive process that involves estimating the duration of an interval over several seconds or minutes. Patients with Alzheimer's disease (AD) have deficits in interval timing. Since temporal control of action is highly conserved across mammalian species, studying interval timing tasks in animal AD models may be relevant to human disease.

Quantifying the inverted U: A meta-analysis of prefrontal dopamine, D1 receptors, and working memory.

Dopamine in the prefrontal cortex can be disrupted in human disorders that affect cognitive function such as Parkinson's disease (PD), attention-deficit hyperactivity disorder (ADHD), and schizophrenia. Dopamine has a powerful effect on prefrontal circuits via the D1-type dopamine receptor (D1DR). It has been proposed that prefrontal dopamine has "inverted U-shaped" dynamics, with optimal dopamine and D1DR signaling required for peak cognitive function.

Temporal Learning Among Prefrontal and Striatal Ensembles.

Behavioral flexibility requires the prefrontal cortex and striatum, but it is unclear if these structures play similar or distinct roles in adapting to novel circumstances. Here, we investigate neuronal ensembles in the medial frontal cortex (MFC) and the dorsomedial striatum (DMS) during one form of behavioral flexibility: learning a new temporal interval. We studied corticostriatal neuronal activity as rodents trained to respond after a 12-s fixed interval (FI12) learned to respond at a shorter 3-s fixed interval (FI3).

Experience-related enhancements in striatal temporal encoding.

Temporal control of action is key for a broad range of behaviors and is disrupted in human diseases such as Parkinson's disease and schizophrenia. A brain structure that is critical for temporal control is the dorsal striatum. Experience and learning can influence dorsal striatal neuronal activity, but it is unknown how these neurons change with experience in contexts which require precise temporal control of movement.

Medial prefrontal cortex and the temporal control of action.

Across species, the medial prefrontal cortex guides actions in time. This process can be studied using behavioral paradigms such as simple reaction-time and interval-timing tasks. Temporal control of action can be influenced by prefrontal neurotransmitters such as dopamine and acetylcholine and is highly relevant to human diseases such as Parkinson's disease, schizophrenia, and attention-deficit hyperactivity disorder (ADHD).

Corticosterone in the ventral hippocampus differentially alters accumbal dopamine output in drug-naïve and amphetamine-withdrawn rats.

Dysregulation in glucocorticoid stress and accumbal dopamine reward systems can alter reward salience to increase motivational drive in control conditions while contributing to relapse during drug withdrawal. Amphetamine withdrawal is associated with dysphoria and stress hypersensitivity that may be mediated, in part, by enhanced stress-induced corticosterone observed in the ventral hippocampus. Electrical stimulation of the ventral hippocampus enhances accumbal shell dopamine release, establishing a functional connection between these two regions.

River metrics by the public, for the public.

Managing rivers in society's best interest requires data on river condition. However, the complexity of river ecosystems, combined with finite budgets for river monitoring and modeling, mean difficult choices are necessary regarding what information will be available. Typically, decisions of "what to measure" are left to natural scientists.

Enhanced dopamine D2 autoreceptor function in the adult prefrontal cortex contributes to dopamine hypoactivity following adolescent social stress.

Adult psychiatric disorders characterized by cognitive deficits reliant on prefrontal cortex (PFC) dopamine are promoted by teenage bullying. Similarly, male Sprague-Dawley rats exposed to social defeat in mid-adolescence (P35-39) show impaired working memory in adulthood (P56-70), along with decreased medial PFC (mPFC) dopamine activity that results in part from increased dopamine transporter-mediated clearance. Here, we determined if dopamine synthesis and D2 autoreceptor-mediated inhibition of dopamine release in the adult mPFC are also enhanced by adolescent defeat to contribute to later dopamine hypofunction.

Impact of juvenile chronic stress on adult cortico-accumbal function: Implications for cognition and addiction.

Repeated exposure to stress during childhood is associated with increased risk for neuropsychiatric illness, substance use disorders and other behavioral problems in adulthood. However, it is not clear how chronic childhood stress can lead to emergence of such a wide range of symptoms and disorders in later life. One possible explanation lies in stress-induced disruption to the development of specific brain regions associated with executive function and reward processing, deficits in which are common to the disorders promoted by childhood stress.

Rivers and streams in the media: a content analysis of ecosystem services.

Although ecosystem services research has become common, few efforts are directed toward in-depth understanding of the specific ecological quantities people value. The theoretical framework of final ecosystem services focuses attention on such measurable attributes, as a common currency for social-ecological systems research. Environmental communications as well as ecological monitoring and analysis efforts could be enhanced through increased documentation of final ecosystem services.