Medial prefrontal cortex (mPFC) interacts with distributed networks that give rise to goal-directed behavior through afferent and efferent connections with multiple thalamic nuclei and recurrent basal ganglia-thalamocortical circuits. Recent studies have revealed individual roles for different thalamic nuclei: mediodorsal (MD) regulation of signaling properties in mPFC neurons, intralaminar control of cortico-basal ganglia networks, ventral medial facilitation of integrative motor function, and hippocampal functions supported by ventral midline and anterior nuclei. Large scale mapping studies have identified functionally distinct cortico-basal ganglia-thalamocortical subnetworks that provide a structural basis for understanding information processing and functional heterogeneity within the basal ganglia.
View Article and Find Full Text PDFBackground: The clearance of solutes removed by tubular secretion may be altered out of proportion to the GFR in CKD. Recent studies have described considerable variability in the secretory clearance of waste solutes relative to the GFR in patients with CKD.
Methods: To test the hypothesis that secretory clearance relative to GFR is reduced in patients approaching dialysis, we used metabolomic analysis to identify solutes in simultaneous urine and plasma samples from 16 patients with CKD and an eGFR of 7±2 ml/min per 1.
The medial prefrontal cortex (mPFC) has robust afferent and efferent connections with multiple nuclei clustered in the central thalamus. These nuclei are elements in large-scale networks linking mPFC with the hippocampus, basal ganglia, amygdala, other cortical areas, and visceral and arousal systems in the brainstem that give rise to adaptive goal-directed behavior. Lesions of the mediodorsal nucleus (MD), the main source of thalamic input to middle layers of PFC, have limited effects on delayed conditional discriminations, like DMTP and DNMTP, that depend on mPFC.
View Article and Find Full Text PDFPruritus is a common debilitating symptom experienced by hemodialysis patients. Treatment is difficult because the cause of uremic pruritus is not known. This study addressed the hypothesis that pruritus is caused by solutes that accumulate in the plasma when the kidneys fail.
View Article and Find Full Text PDFBackground: Impairment of kidney function is routinely assessed by measuring the accumulation of creatinine, an organic solute cleared largely by glomerular filtration. We tested whether the clearance of solutes that undergo tubular secretion is reduced in proportion to the clearance of creatinine in humans with AKI.
Methods: Four endogenously produced organic solutes (phenylacetylglutamine [PAG], hippurate [HIPP], indoxyl sulfate [IS], and p-cresol sulfate [PCS]) were measured in spot urine and plasma samples from ten patients with AKI and 17 controls.
The ability to choose between response alternatives based on their likely consequences depends on distributed neural circuits that involve rodent medial prefrontal cortex (mPFC). To understand the effects of choice on mPFC function, we compared the activity of mPFC neurons in rats performing two tasks: dynamic delayed nonmatching to position (dDNMTP), a task with a prefrontal-dependent conditional choice, and serial lever pressing (SLP), a task lacking a choice but trained in the same apparatus with sequences of actions and reinforcements matched to dDNMTP. More neurons exhibited event-related responses during dDNMTP than SLP.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
August 2019
The accumulation of uremic solutes in kidney failure may impair mental function. The present study profiled the accumulation of uremic solutes in the cerebrospinal fluid (CSF) in acute renal failure. CSF and plasma ultrafiltrate were obtained from rats at 48 h after sham operation (control; = 10) or bilateral nephrectomy ( = 10) and analyzed using an established metabolomic platform.
View Article and Find Full Text PDFThe mediodorsal (MD) and adjacent intralaminar (IL) and midline nuclei provide the main thalamic input to the medial prefrontal cortex (mPFC) and are critical for associative learning and decision-making. MD neurons exhibit activity related to actions and outcomes that mirror responses of mPFC neurons in rats during dynamic delayed non-match to position (dDNMTP), a variation of DNMTP where start location is varied randomly within an open octagonal arena to avoid confounding behavioral events with spatial location. To test whether the thalamus affects the expression of these responses in mPFC, we inhibited the central thalamus unilaterally by microinjecting muscimol at doses and sites found to affect decision-making when applied bilaterally.
View Article and Find Full Text PDFBackground And Objectives: Colon microbial metabolism produces solutes that are normally excreted in the urine and accumulate in the plasma when the kidneys fail. This study sought to further identify and characterize human colon-derived uremic solutes.
Design, Setting, Participants, & Measurements: Colon-derived solutes normally excreted in the urine were identified by comparing urine from controls (=17) and patients with total colectomies (=12), using an established metabolomic platform.
Uremic solutes contribute to cardiovascular disease in renal insufficiency. In this review we describe the clearance of selected uremic solutes, which have been associated with cardiovascular disease. These solutes-indoxyl sulfate (IS), p-cresol sulfate (PCS), phenylacetylglutamine (PAG), trimethylamine-n-oxide (TMAO), and kynurenine-exemplify different mechanisms of clearance.
View Article and Find Full Text PDFBackground: To respond adaptively in a dynamic environment, it is important for organisms to utilise information about recent events to decide between response options.
Methods: To examine the role of medial prefrontal cortex in adaptive decision-making, we recorded single neuron activity in rats performing a dynamic delayed non-matching to position task.
Results: We recorded activity from 1335 isolated neurons, 458 (34%) with criterion event-related activity, of which 431 (94%) exhibited 1 of 10 distinct excitatory response types: five at different times relative to delivery (or lack) of reinforcement following sample and choice responses and five correlated with movements or lever press actions that occurred multiple times in each trial.
The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making.
View Article and Find Full Text PDFThe medial prefrontal cortex has been shown to play a role for rodents in successful completion of tasks that require spatial memory, but the pathways responsible for the transmission of spatial information to the mPFC, and the nature and timing of such information, are unknown. Recently, Spellman, Rigotti, Ahmari, Fusi, Gogos, and Gordon (Nature, 522, 309-314, 2015) addressed these questions in an eloquent and ingenious series of experiments, which we review in the broader context of the neurobiology of spatial memory.
View Article and Find Full Text PDFTo respond adaptively to change organisms must utilize information about recent events and environmental context to select actions that are likely to produce favorable outcomes. We developed a dynamic delayed nonmatching to position task to study the influence of spatial context on event-related activity of medial prefrontal cortex neurons during reinforcement-guided decision-making. We found neurons with responses related to preparation, movement, lever press responses, reinforcement, and memory delays.
View Article and Find Full Text PDFAlthough medial thalamus is well established as a site of pathology associated with global amnesia, there is uncertainty about which structures are critical and how they affect memory function. Evidence from human and animal research suggests that damage to the mammillothalamic tract and the anterior, mediodorsal (MD), midline (M), and intralaminar (IL) nuclei contribute to different signs of thalamic amnesia. Here we focus on MD and the adjacent M and IL nuclei, structures identified in animal studies as critical nodes in prefrontal cortex (PFC)-related pathways that are necessary for delayed conditional discrimination.
View Article and Find Full Text PDFThe main impetus for a mini-symposium on corticothalamic interrelationships was the recent number of studies highlighting the role of the thalamus in aspects of cognition beyond sensory processing. The thalamus contributes to a range of basic cognitive behaviors that include learning and memory, inhibitory control, decision-making, and the control of visual orienting responses. Its functions are deeply intertwined with those of the better studied cortex, although the principles governing its coordination with the cortex remain opaque, particularly in higher-level aspects of cognition.
View Article and Find Full Text PDFClin Gastroenterol Hepatol
December 2012
Background & Aims: We aimed to identify risk factors for hepatocellular carcinoma (HCC) in patients with cirrhosis in the United States. We performed a prospective study to identify associations between etiologies of cirrhosis and ethnicity with HCC incidence.
Methods: We used convenience sampling to select a cohort of 379 patients with cirrhosis who visited the liver clinic at the Stanford University Medical Center from 2001 to 2009 (65% male, 75% white or Hispanic, and 20% Asian).
Central thalamus regulates forebrain arousal, influencing activity in distributed neural networks that give rise to organized actions during alert, wakeful states. Central thalamus has been implicated in working memory by the effects of lesions and microinjected drugs in this part of the brain. Lesions and drugs that inhibit neural activity have been found to impair working memory.
View Article and Find Full Text PDFThe reuniens (Re) and rhomboid (Rh) nuclei are organized to influence activity in distributed limbic networks involving hippocampus and medial prefrontal cortex (mPFC). To elucidate the role of these nuclei in spatial memory we inactivated Re and Rh in rats with the GABA(A) agonist muscimol and compared effects on two spatial delayed conditional discriminations: delayed nonmatching to position (DNMTP) and varying choice radial maze delayed nonmatching (VC-DNM). DNMTP is trained in operant chambers and requires rats to choose between the same two levers on all trials.
View Article and Find Full Text PDFThe reuniens (Re) and rhomboid (Rh) nuclei are major sources of thalamic input to hippocampus and medial prefrontal cortex. We compared effects of lesions in ReRh and other parts of the midline-intralaminar complex on tasks affected by lesions in terminal fields innervated by these nuclei, including: visuospatial reaction time (VSRT), a measure of sensory guided responding; serial VSRT, a measure of action sequence learning; and win/shift radial arm maze (RAM) measures of spatial memory. ReRh lesions affected RAM, but not VSRT or serial VSRT performance.
View Article and Find Full Text PDFInterferon-beta (IFN-beta) is the major treatment for multiple sclerosis. However, this treatment is not always effective. Here we have found congruence in outcome between responses to IFN-beta in experimental autoimmune encephalomyelitis (EAE) and relapsing-remitting multiple sclerosis (RRMS).
View Article and Find Full Text PDFThe rostral intralaminar thalamic nuclei (ILn) are organized to activate pathways originating in medial prefrontal cortex (mPF) that mediate memory-guided responding during alert, wakeful states. Previous studies have shown that rostral ILn or mPF lesions produce deficits in delayed matching to position (DMTP). Here, we manipulated rostral ILn activity in rats by microinjecting drugs or applying electrical current and examined effects on DMTP.
View Article and Find Full Text PDFCentral thalamus has extensive connections with basal ganglia and frontal cortex that are thought to play a critical role in sensory-guided goal-directed behavior. Central thalamic activity is influenced by cholinergic projections from mesopontine nuclei. To elucidate this function we trained rats to respond to lights in a reaction time (RT) task and compared effects of muscarinic (2.
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