Expression pattern of Connexin 26 and Connexin 30 in mature cochlea of the monkey.

Connexin26 (Cx26) and Cx30 are the predominant connexin subtypes found in the cochlea. They play an essential role in the cochlear functions. However, most studies use mice and the data on the cochlear expression profiles of the two Cxs in higher animals (e.

Progressive Assessment of Ischemic Injury to White Matter Using Diffusion Tensor Imaging: A Preliminary Study of a Macaque Model of Stroke.

Background: Previous Diffusion Tensor Imaging (DTI) studies have demonstrated the temporal evolution of stroke injury in grey matter and white matter can be characterized by DTI indices. However, it still remains not fully understood how the DTI indices of white matter are altered progressively during the hyperacute (first 6 hours) and acute stage of stroke (≤ 1 week). In the present study, DTI was employed to characterize the temporal evolution of infarction and white matter injury after stroke insult using a macaque model with permanent ischemic occlusion.

Temporal evolution of ischemic lesions in nonhuman primates: a diffusion and perfusion MRI study.

Background And Purpose: Diffusion-weighted imaging (DWI) and perfusion MRI were used to examine the spatiotemporal evolution of stroke lesions in adult macaques with ischemic occlusion.

Methods: Permanent MCA occlusion was induced with silk sutures through an interventional approach via the femoral artery in adult rhesus monkeys (n = 8, 10-21 years old). The stroke lesions were examined with high-resolution DWI and perfusion MRI, and T2-weighted imaging (T2W) on a clinical 3T scanner at 1-6, 48, and 96 hours post occlusion and validated with H&E staining.

α(2A)-adrenergic receptors filter parabrachial inputs to the bed nucleus of the stria terminalis.

α2-adrenergic receptors (AR) within the bed nucleus of the stria terminalis (BNST) reduce stress-reward interactions in rodent models. In addition to their roles as autoreceptors, BNST α(2A)-ARs suppress glutamatergic transmission. One prominent glutamatergic input to the BNST originates from the parabrachial nucleus (PBN) and consists of asymmetric axosomatic synapses containing calcitonin gene-related peptide (CGRP) and vGluT2.

Ultrastructure of microglia-synapse interactions in the HIV-1 Tat-injected murine central nervous system.

The destruction of normal synaptic architecture is the main pathogenetic substrate in HIV-associated neurocognitive disorder (HAND), but the sequence of cellular events underlying this outcome is not completely understood. Our recent work in a mouse model of HAND using a single intraparenchymal injection of the HIV-1 regulatory protein trans-activator of transcription revealed increased microglial phagocytosis that was accompanied by an increased release of pro-inflammatory cytokines and elimination of dendritic spines in vivo, thus suggesting that microglia-synapse interactions could be dysregulated in HAND. Here, we further examine the relationships between microglia and synaptic structures in our mouse model, at high spatial resolution using immunocytochemical electron microscopy.

Distribution of AMPA receptor subunit glur1 in the bed nucleus of the stria terminalis and effect of stress.

The brain circuitry thought to be involved in stress responses includes several nuclei of the extended amygdala. The bed nucleus of the stria terminalis (BNST) is thought to be involved in the generation of sustained, nonspecific anxiety. Previous behavioral and electrophysiological experiments demonstrate that glutamate systems are involved in anxiety-like behaviors in the BNST.

Memory deficits in aging and neurological diseases.

Memory is central to our ability to perform daily life activities and correctly function in society. Improvements in public health and medical treatment for a variety of diseases have resulted in longer life spans; however, age-related memory impairments have been significant sources of morbidity. Loss in memory function is not only associated with aging population but is also a feature of neurodegenerative diseases such as Alzheimer's disease and other psychiatric and neurological disorders.

Distribution and functional expression of Kv4 family α subunits and associated KChIP β subunits in the bed nucleus of the stria terminalis.

Regulation of BNSTALG neuronal firing activity is tightly regulated by the opposing actions of the fast outward potassium current, IA , mediated by α subunits of the Kv4 family of ion channels, and the transient inward calcium current, IT . Together, these channels play a critical role in regulating the latency to action potential onset, duration, and frequency, as well as dendritic back-propagation and synaptic plasticity. Previously we have shown that Type I-III BNSTALG neurons express mRNA transcripts for each of the Kv4 α subunits.

The new small-molecule mixed-lineage kinase 3 inhibitor URMC-099 is neuroprotective and anti-inflammatory in models of human immunodeficiency virus-associated neurocognitive disorders.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) is a significant source of disability in the HIV-infected population. Even with stringent adherence to anti-retroviral therapy, >50% of patients living with HIV-1 will develop HAND (Heaton et al., 2010).

Effects of stress on AMPA receptor distribution and function in the basolateral amygdala.

Stress is a growing public health concern and can lead to significant disabilities. The neural response to stressors is thought to be dependent on the extended amygdala. The basolateral amygdala (BLA) is responsible for associations of sensory stimuli with emotional valence and is thought to be involved in stress-induced responses.

Schizophrenia: causes and treatments.

Schizophrenia is a major mental illness that is characterized by psychosis, apathy, social withdrawal and cognitive impairment. These abnormalities in patients results in impaired functioning in work, school, parenting, self-care, independent living, interpersonal relationships, and leisure. Although the search for the biological correlates of schizophrenia has met with limited success, new advances in genetics and pharmacology are promising.

Relationship between dose, drug levels, and D2 receptor occupancy for the atypical antipsychotics risperidone and paliperidone.

Blockade of D2 family dopamine receptors (D2Rs) is a fundamental property of antipsychotics, and the degree of striatal D2R occupancy has been related to antipsychotic and motor effects of these drugs. Recent studies suggest the D2R occupancy of antipsychotics may differ in extrastriatal regions compared with the dorsal striatum. We studied this issue in macaque monkeys by using a within-subjects design.

Presynaptic muscarinic M(2) receptors modulate glutamatergic transmission in the bed nucleus of the stria terminalis.

The anterolateral cell group of the bed nucleus of the stria terminalis (BNST(ALG)) serves as an important relay station in stress circuitry. Limbic inputs to the BNST(ALG) are primarily glutamatergic and activity-dependent changes in this input have been implicated in abnormal behaviors associated with chronic stress and addiction. Significantly, local infusion of acetylcholine (ACh) receptor agonists into the BNST trigger stress-like cardiovascular responses, however, little is known about the effects of these agents on glutamatergic transmission in the BNST(ALG).

Molecular mechanisms of working memory.

Working memory is a process for temporary active maintenance of information and the role of prefrontal cortex in this memory has been known since the pioneering experiments of Fulton in the early 20th century. Sustained firing of prefrontal neurons during the delay period is considered the neural correlate of working memory. Evidence in literature suggests the involvement of areas beyond the frontal lobe and illustrate that working memory involves parallel, distributed neuronal networks.

Distribution of D1 and D5 dopamine receptors in the primate nucleus accumbens.

The D1 family of dopamine receptors (D1R) play a critical role in modulating reward in the nucleus accumbens (NAc). A better understanding of how D1Rs modulate NAc function must take into account the contributions of the two D1R subtypes, D(1) and D(5). In order to determine how these two subtypes contribute to dopamine's actions in the NAc, we utilized subtype specific antibodies and immunoelectron microscopy to quantitatively determine the localization of D(1) and D(5) in the neuropil of the primate NAc.

Extracerebellar role for Cerebellin1: modulation of dendritic spine density and synapses in striatal medium spiny neurons.

Cerebellin1 (Cbln1) is a secreted glycoprotein that was originally isolated from the cerebellum and subsequently found to regulate synaptic development and stability. Cbln1 has a heterogeneous distribution in brain, but the only site in which it has been shown to have central effects is the cerebellar cortex, where loss of Cbln1 causes a reduction in granule cell-Purkinje cell synapses. Neurons of the thalamic parafascicular nucleus (PF), which provide glutamatergic projections to the striatum, also express high levels of Cbln1.

Chronic, constant-rate, gastric drug infusion in nontethered rhesus macaques (Macaca mulatta).

As part of a study of antipsychotic drug treatment in monkeys, we developed a technique to provide chronic, constant-rate, gastric drug infusion in nontethered rhesus macaques. This method allowed us to mimic the osmotic release oral delivery system currently used in humans for continuous enteral drug delivery. Rhesus macaques (n = 5) underwent gastric catheter placement by laparotomy.

Localization of dopamine- and cAMP-regulated phosphoprotein-32 and inhibitor-1 in area 9 of Macaca mulatta prefrontal cortex.

The actions of dopamine D1 family receptors (D1R) depend upon a signal transduction cascade that modulates the phosphorylation state of important effector proteins, such as glutamate receptors and ion channels. This is accomplished both through activation of protein kinase A (PKA) and the inhibition of protein phosphatase-1 (PP1). Inhibition of PP1 occurs through PKA-mediated phosphorylation of dopamine- and cAMP-regulated phosphoprotein 32 kDa (DARPP-32) or the related protein inhibitor-1 (I-1), and the availability of DARPP-32 is essential to the functional outcome of D1R activation in the basal ganglia.

Is the loss of thalamostriatal neurons protective in parkinsonism?

Neuronal loss in Parkinson's disease (PD) is more widespread than originally thought. Among the extrastriatal sites in which significant loss of neurons has been reported is the centremedian-parafascicular (CM-PF) complex of the thalamus, which provides one of the three major afferent sources to the striatum. The functional significance of CM-PF loss in PD is unclear.

Distribution of D1 and D5 dopamine receptors in the primate and rat basolateral amygdala.

Dopamine, acting at the D1 family receptors (D1R) is critical for the functioning of the amygdala, including fear conditioning and cue-induced reinstatement of drug self administration. However, little is known about the different contributions of the two D1R subtypes, D(1) and D(5). We identified D(1)-immunoreactive patches in the primate that appear similar to the intercalated cell masses reported in the rodent; however, both receptors were present across the subdivisions of the primate amygdala including the basolateral amygdala (BLA).

Localization of myocyte enhancer factor 2 in the rodent forebrain: regionally-specific cytoplasmic expression of MEF2A.

The transcription factor myocyte enhancer factor 2 (MEF2) is expressed throughout the central nervous system, where four MEF2 isoforms play important roles in neuronal survival and differentiation and in synapse formation and maintenance. It is therefore somewhat surprising that there is a lack of detailed information on the localization of MEF2 isoforms in the mammalian brain. We have analyzed the regional, cellular, and subcellular expression of MEF2A and MEF2D in the rodent brain.

Immunohistochemical characterization of parvalbumin-containing interneurons in the monkey basolateral amygdala.

Interneurons expressing the calcium-binding protein parvalbumin (PV) are a critical component of the inhibitory circuitry of the basolateral nuclear complex (BLC) of the mammalian amygdala. These neurons form interneuronal networks interconnected by chemical and electrical synapses, and provide a strong perisomatic inhibition of local pyramidal projection neurons. Immunohistochemical studies in rodents have shown that most parvalbumin-positive (PV+) cells are GABAergic interneurons that co-express the calcium-binding protein calbindin (CB), but exhibit no overlap with interneuronal subpopulations containing the calcium-binding protein calretinin (CR) or neuropeptides.

Dopamine D1 and D5 receptors are localized to discrete populations of interneurons in primate prefrontal cortex.

Working memory (WM) is a core cognitive process that depends upon activation of D1 family receptors (D1R) and inhibitory interneurons in the prefrontal cortex (PFC). D1R are comprised of the D(1) and D(5) subtypes, and D(5) has a 10-fold higher affinity for dopamine. Parvalbumin (PV) and calretinin (CR) are 2 interneuron populations that are differentially affected by D1R stimulation and have discrete postsynaptic targets, such that PV interneurons provide strong inhibition to pyramidal cells, whereas CR interneurons inhibit other interneurons.

Subcellular distribution of the Rho-GEF Lfc in primate prefrontal cortex: effect of neuronal activation.

The strength of synaptic connections in the brain varies with activity, and this plasticity depends on remodeling of the actin cytoskeleton in dendritic spines. Critical to this are the Rho family GTPases, whose activity is controlled by various modulatory proteins, including the Rho-GEF Lfc. In cultured neurons and nonneuronal cells, Lfc has been shown both to bind to microtubules and to regulate the actin cytoskeleton.