Integrative STEM education for undergraduate neuroscience: Design and implementation.

As an integrative discipline, neuroscience can serve as a vehicle for the development of integrative thinking skills and broad-based scientific proficiency in undergraduate students. Undergraduate neuroscience curricula incorporate fundamental concepts from multiple disciplines. Deepening the explicit exploration of these connections in a neuroscience core curriculum has the potential to support more meaningful and successful undergraduate STEM learning for neuroscience students.

An Integrative Approach to STEM Concepts in an Introductory Neuroscience Course: Gains in Interdisciplinary Awareness.

Neuroscience is an integrative discipline for which students must achieve broad-based proficiency in many of the sciences. We are motivated by the premise that student pursuit of proficiency in science, technology, engineering, and mathematics (STEM) can be supported by awareness of the application of knowledge and tools from the various disciplines for solving complex problems. We refer to this awareness as "interdisciplinary awareness.

Endogenous co-agonists of the NMDA receptor modulate contextual fear in trace conditioning.

We have used mutant mice to probe the roles of the endogenous co-agonists of the NMDA receptor (NMDAR), D-serine and glycine, in fear learning and memory. Serine racemase knockout (SR-/-) mice have less than 15% of wild type forebrain levels of D-serine, whereas glycine transporter 1 heterozygous knockout (GlyT1+/-) mice have elevated synaptic glycine. While cued fear was normal in both delay and trace conditioned mice of both mutant genotypes, contextual fear was affected in trace conditioned subjects: SR-/- mice showed decreased contextual freezing, whereas GlyT1+/- mice showed elevated contextual freezing.

Effects of environmental enrichment on anxiety-like behavior, sociability, sensory gating, and spatial learning in male and female C57BL/6J mice.

The influence of housing on cognition and emotional regulation in mice presents a problem for the study of genetic and environmental risk factors for neuropsychiatric disorders: standard laboratory housing may result in low levels of cognitive function or altered levels of anxiety that leave little room for assessment of deleterious effects of experimental manipulations. The use of enriched environment (EE) may allow for the measurement of a wider range of performance in cognitive domains. Cognitive and behavioral effects of EE in male mice have not been widely reproduced, perhaps due to variability in the application of enrichment protocols, and the effects of EE in female mice have not been widely studied.

Multiple risk pathways for schizophrenia converge in serine racemase knockout mice, a mouse model of NMDA receptor hypofunction.

Schizophrenia is characterized by reduced hippocampal volume, decreased dendritic spine density, altered neuroplasticity signaling pathways, and cognitive deficits associated with impaired hippocampal function. We sought to determine whether this diverse pathology could be linked to NMDA receptor (NMDAR) hypofunction, and thus used the serine racemase-null mutant mouse (SR(-/-)), which has less than 10% of normal brain D-serine, an NMDAR coagonist. We found that D-serine was necessary for the maintenance of long-term potentiation in the adult hippocampal dentate gyrus and for full NMDAR activity on granule cells.

Time-dependent effects of haloperidol on glutamine and GABA homeostasis and astrocyte activity in the rat brain.

Rationale: Schizophrenia is a severe, persistent, and fairly common mental illness. Haloperidol is widely used and is effective against the symptoms of psychosis seen in schizophrenia. Chronic oral haloperidol administration decreased the number of astrocytes in the parietal cortex of macaque monkeys (Konopaske et al.

Identity of endogenous NMDAR glycine site agonist in amygdala is determined by synaptic activity level.

Mechanisms of N-methyl-D-aspartate receptor-dependent synaptic plasticity contribute to the acquisition and retention of conditioned fear memory. However, synaptic rules which may determine the extent of N-methyl-D-aspartate receptor activation in the amygdala, a key structure implicated in fear learning, remain unknown. Here we show that the identity of the N-methyl-D-aspartate receptor glycine site agonist at synapses in the lateral nucleus of the amygdala may depend on the level of synaptic activation.

Cell selective conditional null mutations of serine racemase demonstrate a predominate localization in cortical glutamatergic neurons.

D-serine, which is synthesized by the enzyme serine racemase (SR), is a co-agonist at the N-methyl-D-aspartate receptor (NMDAR). Crucial to an understanding of the signaling functions of D-serine is defining the sites responsible for its synthesis and release. In order to quantify the contributions of astrocytes and neurons to SR and D-serine localization, we used recombinant DNA techniques to effect cell type selective suppression of SR expression in astrocytes (aSRCKO) and in forebrain glutamatergic neurons (nSRCKO).

The NMDA receptor co-agonists, D-serine and glycine, regulate neuronal dendritic architecture in the somatosensory cortex.

There is substantial evidence, both pharmacological and genetic, that hypofunction of the N-methyl-d-aspartate receptor (NMDAR) is a core pathophysiological feature of schizophrenia. There are morphological brain changes associated with schizophrenia, including perturbations in the dendritic morphology of cortical pyramidal neurons and reduction in cortical volume. Our experiments investigated whether these changes in dendritic morphology could be recapitulated in a genetic model of NMDAR hypofunction, the serine racemase knockout (SR-/-) mouse.

Failure of NMDA receptor hypofunction to induce a pathological reduction in PV-positive GABAergic cell markers.

Reduction in cortical presynaptic markers, notably parvalbumin (PV), for the chandelier subtype of inhibitory γ-amino-butyric acid (GABA) interneurons is a highly replicated post-mortem finding in schizophrenia. Evidence from genetic and pharmacological studies implicates hypofunction of N-methyl-d-aspartate receptor (NMDAR)-mediated glutamatergic signaling as a critical component of the pathophysiology of schizophrenia. Serine racemase (SR) produces the endogenous NMDAR co-agonist d-serine, and disruption of the SR gene results in reduced NMDAR signaling.

Discordant behavioral effects of psychotomimetic drugs in mice with altered NMDA receptor function.

Rationale: Enhancement of N-methyl-D: -aspartate receptor (NMDAR) activity through its glycine modulatory site (GMS) is a novel therapeutic approach in schizophrenia. Brain concentrations of endogenous GMS agonist D: -serine and antagonist N-acetyl-aspartylglutamate are regulated by serine racemase (SR) and glutamic acid decarboxylase 2 (GCP2), respectively. Using mice genetically, under-expressing these enzymes may clarify the role of NMDAR-mediated neurotransmission in schizophrenia.

Phenotypic characterization of mice heterozygous for a null mutation of glutamate carboxypeptidase II.

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Disturbed glutamate signaling resulting in hypofunction of N-methyl-D-aspartate receptors (NMDAR) has been implicated in the pathophysiology of schizophrenia. Glutamate Carboxypeptidase II (GCP II) hydrolyzes N-acetyl-alpha L-aspartyl-L-glutamate (NAAG) into glutamate and N-acetyl-aspartate.

Ube3a mRNA and protein expression are not decreased in Mecp2R168X mutant mice.

Mutations in the transcriptional repressor methyl CpG binding protein 2 (MeCP2) are responsible for most cases of Rett Syndrome (RS), a severe neurodevelopmental disorder characterized by developmental regression, minimal speech, seizures, postnatal microcephaly and hand stereotypies. Absence of the maternal copy of ubiquitin protein ligase 3A (UBE3A) results in Angelman syndrome, also a severe developmental disorder that shares some clinical features with RS. As MeCP2 regulates gene expression, this has led to the hypothesis that MeCP2 may regulate UBE3A expression; however, there are conflicting reports regarding the expression of Ube3a in MeCP2 null mutant mice.

Learning and memory associated with aggression in Drosophila melanogaster.

Male Drosophila melanogaster (Canton-S strain) exhibit aggression in competition for resources, to defend territory, and for access to mates. In the study reported here, we asked: (i) how long flies fight; (ii) whether flies adopt distinct winning and losing strategies as hierarchical relationships are established; (iii) whether flies exhibit experience-dependent changes in fighting strategies in later fights; and (iv) whether flies fight differently in second fights against familiar or unfamiliar opponents. The results showed that flies fought for up to 5 h.

Changes in heart rate associated with contest outcome in agonistic encounters in lobsters.

Agonistic contests between lobsters housed together in a confined space progress through encounters of increasing intensity until a dominance relationship is established. Once this relationship is established, losing animals continually retreat from the advances of winners. These encounters are likely to consume much energy in both winning and losing animals.

Morphology and monoaminergic modulation of Crustacean Hyperglycemic Hormone-like immunoreactive neurons in the lobster nervous system.

Neuronal somata located near branch points in the second thoracic nerve roots of the lobster are immunoreactive for Crustacean Hyperglycemic Hormone (CHH)-like peptides, a family of putative stress hormones. We have employed intracellular dye injection, immunostaining, and confocal imaging to observe the anatomy of these root neurons, which are morphologically diverse and dye coupled. Some root neurons contribute to neurosecretory structures at the points of exit of the root from the nerve cord.