Search PubMed⌕ Search

Biomedical subjects

Amy Bernard

Publications and source records attributed to Amy Bernard.

4 recordsLinked to original sources

Genome-wide atlas of gene expression in the adult mouse brain.

Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.

Animals↗

Expression of GABA(B) receptor in the avian auditory brainstem: ontogeny, afferent deprivation, and ultrastructure.

Nucleus magnocellularis (NM), nucleus angularis (NA), and nucleus laminaris (NL), second- and third-order auditory neurons in the avian brainstem, receive GABAergic input primarily from the superior olivary nucleus (SON). Previous studies have demonstrated that both GABA(A) and GABA(B) receptors (GABA(B)Rs) influence physiological properties of NM neurons. We characterized the distribution of GABA(B)R expression in these nuclei during development and after deafferentation of the excitatory auditory nerve (nVIII) inputs. We used a polyclonal antibody raised against rat GABA(B)Rs in the auditory brainstem during developmental periods that are thought to precede and include synaptogenesis of GABAergic inputs. As early as embryonic day (E)14, dense labeling is observed in NA, NM, NL, and SON. At earlier ages immunoreactivity is present in somas as diffuse staining with few puncta. By E21, when the structure and function of the auditory nuclei are known to be mature, GABA(B) immunoreactivity is characterized by dense punctate labeling in NM, NL, and a subset of NA neurons, but label is sparse in the SON. Removal of the cochlea and nVIII neurons in posthatch chicks resulted in only a small decrease in immunoreactivity after survival times of 14 or 28 days, suggesting that a major proportion of GABA(B)Rs may be expressed postsynaptically or on GABAergic terminals. We confirmed this interpretation with immunogold TEM, where expression at postsynaptic membrane sites is clearly observed. The characterization of GABA(B)R distribution enriches our understanding of the full complement of inhibitory influences on central auditory processing in this well-studied neuronal circuit.

Animals↗

Assessing progress in analysis interminable.

A case study is provided of a schizoid patient in her mid-sixties who in a lengthy analysis had made significant clinical improvement. The treating analyst's impression of clinical improvement was independently verified through systematic analysis of transcripts of audiotapes of thirty-six sessions over a four-year period of treatment. The patient showed significant improvement on measures of character pathology, object relations, mentalization, and superego anxiety. The results suggest that some patients with entrenched character pathology who seem to be in analysis interminable may still make clinically significant improvement. It is suggested that the scientific status of psychoanalysis would be greatly enhanced if the anecdotal evidence generated in private practice were supported by independent verification. The current study illustrates one methodology, "case study plus," for providing independent verification while retaining the richness of the traditional case study.

Female↗

Wnt signaling is required at distinct stages of development for the induction of the posterior forebrain.

One of the earliest manifestations of anteroposterior pattering in the developing brain is the restricted expression of Six3 and Irx3 in the anterior and posterior forebrain, respectively. Consistent with the role of Wnts as posteriorizing agents in neural tissue, we found that Wnt signaling was sufficient to induce Irx3 and repress Six3 expression in forebrain explants. The position of the zona limitans intrathalamica (zli), a boundary-cell population that develops between the ventral (vT) and dorsal thalamus (dT), is predicted by the apposition of Six3 and Irx3 expression domains. The expression patterns of several inductive molecules are limited by the zli, including Wnt3, which is expressed posterior to the zli in the dT. Wnt3 and Wnt3a were sufficient to induce the dT marker Gbx2 exclusively in explants isolated posterior to the presumptive zli. Blocking the Wnt response allowed the induction of the vT-specific marker Dlx2 in prospective dT tissue. Misexpression of Six3 in the dT induced Dlx2 expression and inhibited the expression of both Gbx2 and Wnt3. These results demonstrate a dual role for Wnt signaling in forebrain development. First, Wnts directed the initial expression of Irx3 and repression of Six3 in the forebrain, delineating posterior and anterior forebrain domains. Later, continued Wnt signaling resulted in the induction of dT specific markers, but only in tissues that expressed Irx3.

Animals↗