Changes in the dopaminergic circuitry and adult neurogenesis linked to reinforcement learning in corvids.

The caudolateral nidopallium (NCL, an analog of the prefrontal cortex) is known to be involved in learning, memory, and discrimination in corvids (a songbird), whereas the involvement of other brain regions in these phenomena is not well explored. We used house crows () to explore the neural correlates of learning and decision-making by initially training them on a shape discrimination task followed by immunohistochemistry to study the immediate early gene expression (Arc), a dopaminoceptive neuronal marker (DARPP-32, Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa) to understand the involvement of the reward pathway and an immature neuronal marker (DCX, doublecortin) to detect learning-induced changes in adult neurogenesis. We performed neuronal counts and neuronal tracing, followed by morphometric analyses.

The Role of the Endogenous Opioid System in the Vocal Behavior of Songbirds and Its Possible Role in Vocal Learning.

The opioid system in the brain is responsible for processing affective states such as pain, pleasure, and reward. It consists of three main receptors, mu- (μ-ORs), delta- (δ-ORs), and kappa- (κ-ORs), and their ligands - the endogenous opioid peptides. Despite their involvement in the reward pathway, and a signaling mechanism operating in synergy with the dopaminergic system, fewer reports focus on the role of these receptors in higher cognitive processes.

The expression of delta opioid receptor mRNA in adult male zebra finches (Taenopygia guttata).

The endogenous opioid system is evolutionarily conserved across reptiles, birds and mammals and is known to modulate varied brain functions such as learning, memory, cognition and reward. To date, most of the behavioral and anatomical studies in songbirds have mainly focused on μ-opioid receptors (ORs). Expression patterns of δ-ORs in zebra finches, a well-studied species of songbird have not yet been reported, possibly due to the high sequence similarity amongst different opioid receptors.

Investigating Behavioral Responses to Mirrors and the Mark Test in Adult Male Zebra Finches and House Crows.

Earlier evidence suggests that besides humans, some species of mammals and birds demonstrate visual self-recognition, assessed by the controversial "mark" test. Whereas, there are high levels of inter-individual differences amongst a single species, some species such as macaques and pigeons which do not spontaneously demonstrate mirror self-recognition (MSR) can be trained to do so. We were surprised to discover that despite being widely used as a model system for avian research, the performance of zebra finches () on the mark test had not been studied earlier.

Blocking Opioid Receptors in a Songbird Cortical Region Modulates the Acoustic Features and Levels of Female-Directed Singing.

The organization of the anterior forebrain pathway (AFP) of songbirds important for context-dependent singing is similar to that of cortical basal ganglia loops (CBG) in mammals, which underlie motor behaviors including vocalization. Since different components of the AFP express high levels of μ-opioid receptors (μ-ORs) as do CBG loops, songbirds act as model systems to study the role of opioid modulation on vocalization and the motivation to sing. The AFP in songbirds includes the cortical/pallial region LMAN (lateral magnocellular nucleus of the anterior nidopallium) which projects to Area X, a nucleus of the avian basal ganglia.

The expression of DARPP-32 in adult male zebra finches (Taenopygia guttata).

Although the catecholaminergic circuitry in the zebra finch brain has been well studied, there is little information regarding the postsynaptic targets of dopamine. To answer this question, we looked at overall patterns of immunoreactivity for DARPP-32 (a dopamine and cAMP-regulated phosphoprotein, present mostly in dopaminoceptive neurons) in adult male zebra finches. Our results demonstrated that as in mammals and other avian species, DARPP-32 expression was highest in both medial and lateral striatum.

Altering Opioid Neuromodulation in the Songbird Basal Ganglia Modulates Vocalizations.

Although the interplay between endogenous opioids and dopamine (DA) in the basal ganglia (BG) is known to underlie diverse motor functions, few studies exist on their role in modulating speech and vocalization. Vocal impairment is a common symptom of Parkinson's disease (PD), wherein DA depletion affects striosomes rich in μ-opioid receptors (μ-ORs). Symptoms of opioid addiction also include deficiencies in verbal functions and speech.

The expression of tyrosine hydroxylase and DARPP-32 in the house crow (Corvus splendens) brain.

Birds of the family Corvidae which includes diverse species such as crows, rooks, ravens, magpies, jays, and jackdaws are known for their amazing abilities at problem-solving. Since the catecholaminergic system, especially the neurotransmitter dopamine, plays a role in cognition, we decided to study the distribution of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamines in the brain of house crows (Corvus splendens). We also studied the expression of DARPP-32 (dopamine and cAMP-regulated phosphoprotein), which is expressed in dopaminoceptive neurons.

Method for improving the quality of genomic DNA obtained from minute quantities of tissue and blood samples using Chelex 100 resin.

Background: Although genomic DNA isolation using the Chelex 100 resin is rapid and inexpensive, the DNA obtained by this method has a low concentration in solution and contains suspended impurities. The presence of debris in the DNA solution may result in degradation of DNA on long term storage and inhibition of the polymerase chain reaction. In order to remove impurities and concentrate the DNA in solution, we have introduced modifications in the existing DNA isolation protocol using Chelex-100.

Growth and refinement of excitatory synapses in the human auditory cortex.

We had earlier demonstrated a neurofilament-rich plexus of axons in the presumptive human auditory cortex during fetal development which became adult-like during infancy. To elucidate the origin of these axons, we studied the expression of the vesicular glutamate transporters (VGLUT) 1 and 2 in the human auditory cortex at different stages of development. While VGLUT-1 expression predominates in intrinsic and cortico-cortical synapses, VGLUT-2 expression predominates in thalamocortical synapses.

Neuronatin-mediated aberrant calcium signaling and endoplasmic reticulum stress underlie neuropathology in Lafora disease.

Lafora disease (LD) is a teenage-onset inherited progressive myoclonus epilepsy characterized by the accumulations of intracellular inclusions called Lafora bodies and caused by mutations in protein phosphatase laforin or ubiquitin ligase malin. But how the loss of function of either laforin or malin causes disease pathogenesis is poorly understood. Recently, neuronatin was identified as a novel substrate of malin that regulates glycogen synthesis.

Expression of medium and heavy chain neurofilaments in the developing human auditory cortex.

Neurofilament medium (NF-M) and heavy (NF-H) chain proteins have been used as markers for maturity in the developing brain since their accumulation in axons leads to an increase in conduction velocity. Earlier studies have demonstrated immunoreactivity of neurofilaments in Layer I of the human auditory cortex at 22 gestation weeks (GW), whereas that in other layers developed between 1 and 12 postnatal years, suggesting a gradual increase in the processing of sounds. However, third trimester fetuses and infants are fairly sophisticated in their ability to discern different aspects of complex sounds.

Preterm delivery disrupts the developmental program of the cerebellum.

A rapid growth in human cerebellar development occurs in the third trimester, which is impeded by preterm delivery. The goal of this study was to characterize the impact of preterm delivery on the developmental program of the human cerebellum. Still born infants, which meant that all development up to that age had taken place in-utero, were age paired with preterm delivery infants, who had survived in an ex-utero environment, which meant that their development had also taken place outside the uterus.

Expression of Sonic hedgehog during cell proliferation in the human cerebellum.

The regulation of cell proliferation in the external granular layer (EGL) of the developing cerebellum is important for its normal patterning. An important signal that regulates EGL cell proliferation is Sonic hedgehog (Shh). Shh is secreted by the Purkinje cells (PC) and has a mitogenic effect on the granule cell precursors of the EGL.

Opioid modulation of cell proliferation in the ventricular zone of adult zebra finches (Taenopygia guttata).

Besides modulating pain, stress, physiological functions, motivation, and reward, the opioid system has been implicated in developmental and adult mammalian neurogenesis and gliogenesis. In adult male songbirds including zebra finches, neurons generated from the ventricular zone (VZ) of the lateral ventricles are incorporated throughout the telencephalon, including the song control nuclei, HVC, and area X. Although the endogenous opioid met-enkephalin is present in neurons adjacent to the VZ and is upregulated in song control regions during singing, it is not known whether the opioid system can modulate adult neurogenesis/gliogenesis in zebra finches.

Opioid modulation of song in male zebra finches (Taenopygia guttata).

Endogenous opioids are known to modulate motivated behaviors. Male zebra finches produce a highly motivated behavior (directed song) to court females and also sing in isolation (undirected song). We found that adult male zebra finches sang significantly fewer directed and undirected songs after administration of low doses (2.

Expression of mu- and delta-opioid receptors in song control regions of adult male zebra finches (Taenopygia guttata).

The opioid system is known to play a role in various aspects of learning and memory in diverse species of mammals and birds. Earlier studies have localized the endogenous opioids, met- and leu-enkephalin, in the song control regions of male zebra finches (Taenopygia guttata), a sexually dimorphic species of songbirds wherein only males sing. Recent research has shown that levels of enkephalin increase in some of the song control regions during singing and that blocking opioid receptors with the antagonist naloxone decreases the frequency of singing in songbirds.

Expression of delta- and mu-opioid receptors in the ventricular and subventricular zones of the developing human neocortex.

Recent research has documented the involvement of the endogenous opioid system in neural development, including neurogenesis and neuronal differentiation. However, the expression of opioid receptors (ORs) in different cell types of the human ventricular and subventricular zones (VZ and SVZ) has not been studied during early gestation. In the present study, we have used immunohistochemistry and quantified the results to demonstrate that the levels of delta- and mu-OR subtypes were high in the VZ and SVZ between 11 and 16 gestation weeks (GW) and decreased by 20GW.

Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of death-associated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson's disease: protection by alpha-lipoic acid.

Parkinson's disease (PD), a neurodegenerative disorder, causes severe motor impairment due to loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). MPTP, a neurotoxin that causes dopaminergic cell loss in mice, was used in an animal model to study the pathogenic mechanisms leading to neurodegeneration. We observed the activation of apoptosis signal regulating kinase (ASK1, MAPKKK) and phosphorylation of its downstream targets MKK4 and JNK, 12 h after administration of a single dose of MPTP.

Cortical and thalamic connections of the representations of the teeth and tongue in somatosensory cortex of new world monkeys.

Connections of representations of the teeth and tongue in primary somatosensory cortex (area 3b) and adjoining cortex were revealed in owl, squirrel, and marmoset monkeys with injections of fluorescent tracers. Injection sites were identified by microelectrode recordings from neurons responsive to touch on the teeth or tongue. Patterns of cortical label were related to myeloarchitecture in sections cut parallel to the surface of flattened cortex, and to coronal sections of the thalamus processed for cytochrome oxidase (CO).

Cortical network for representing the teeth and tongue in primates.

Sensory information from the tongue and teeth is used to evaluate and distinguish food and nonfood items in the mouth, reject some and masticate and swallow others. While it is known that primates have a complex array of 10 or more somatosensory areas that contribute to the analysis of sensory information from the hand, less is known about what cortical areas are involved in processing information from receptors of the tongue and teeth. The tongue contains taste receptors, as well as mechanoreceptors.

The role of auditory experience in the formation of neural circuits underlying vocal learning in zebra finches.

The initial establishment of topographic mapping within developing neural circuits is thought to be shaped by innate mechanisms and is primarily independent of experience. Additional refinement within topographic maps leads to precise matching between presynaptic and postsynaptic neurons and is thought to depend on experiential factors during specific sensitive periods in the animal's development. In male zebra finches, axonal projections of the cortical lateral magnocellular nucleus of the anterior neostriatum (lMAN) are critically important for vocal learning.

Development of individual axon arbors in a thalamocortical circuit necessary for song learning in zebra finches.

Individual axon arbors within developing neural circuits are remodeled during restricted sensitive periods, leading to the emergence of precise patterns of connectivity and specialized adaptive behaviors. In male zebra finches, the circuit connecting the medial dorsolateral nucleus of the thalamus (DLM) and its cortical target, the lateral magnocellular nucleus of the anterior neostriatum (lMAN), is crucial for the acquisition of a normal vocal pattern during the sensitive period for song learning. The shell subregion of lMAN as well as the entire terminal field of DLM axons within lMAN undergo a striking increase in overall volume during early stages of vocal learning followed by an equally substantial decrease by adulthood, by which time birds have acquired stable song patterns.