Human-Specific Transcriptional Networks in the Brain

Konopka, Genevieve; Friedrich, Tara; Davis-Turak, Jeremy; Winden, Kellen D.; Oldham, Michael C.; Gao, Fuying; Chen, Leslie; Wang, Guang Zhong; Luo, Rui; Preuss, Todd M.; Geschwind, Daniel H.

doi:10.1016/j.neuron.2012.05.034

Cited by 238 publications

(283 citation statements)

References 87 publications

Supporting

Mentioning

253

Contrasting

Order By: Relevance

“…Ryan et al, 2013). Furthermore, evolutionary developments involving expression of genes affecting NMDAR function have occurred specifically in the human lineage within the last six million years (Konopka et al, 2012). The cognitive functions affected by these mutations are likely to involve contextual modulation, and this inference is supported by their strong association with schizophrenia in humans .…”

Section: Are There Major Transitions In the Evolution Of Inferentialmentioning

confidence: 99%

On the functions, mechanisms, and malfunctions of intracortical contextual modulation

Phillips

Clark

Silverstein

2015

Neuroscience & Biobehavioral Reviews

View full text Add to dashboard Cite

A broad neuron-centric conception of contextual modulation is reviewed and re-assessed in the light of recent neurobiological studies of amplification, suppression, and synchronization. Behavioural and computational studies of perceptual and higher cognitive functions that depend on these processes are outlined, and evidence that those functions and their neuronal mechanisms are impaired in schizophrenia is summarized. Finally, we compare and assess the long-term biological functions of contextual modulation at the level of computational theory as formalized by the theories of coherent infomax and free energy reduction. We conclude that those theories, together with the many empirical findings reviewed, show how contextual modulation at the neuronal level enables the cortex to flexibly adapt the use of its knowledge to current circumstances by amplifying and grouping relevant activities and by suppressing irrelevant activities.

show abstract

Section: Are There Major Transitions In the Evolution Of Inferentialmentioning

confidence: 99%

On the functions, mechanisms, and malfunctions of intracortical contextual modulation

Phillips

Clark

Silverstein

2015

Neuroscience & Biobehavioral Reviews

View full text Add to dashboard Cite

show abstract

“…T e relative uniqueness of the human brain creates high hurdles for development of animal models. Anatomically, much of the neural circuitry involved in psychiatric symptoms-for example, that of the prefrontal cerebral cortex-is new or vastly expanded in humans, and gene expression patterns in the human cerebral cortex also appear to be newly evolved, even compared with nonhuman primates (24). T at said, for neural circuits that are conserved in evolution-those involved in basic emotions such as fear and reward as well as some basic cognitive functions-rodents and other organisms can potentially provide useful preclinical models (16,25).…”

Section: Mind the Gapmentioning

confidence: 99%

Revolution Stalled

2012

View full text Add to dashboard Cite

Drug discovery is at a near standstill for treating psychiatric disorders such as schizophrenia, bipolar disorder, depression, and common forms of autism. Despite high prevalence and unmet medical need, major pharmaceutical companies are deemphasizing or exiting psychiatry, thus removing signif cant capacity from ef orts to discover new medicines. In this Commentary, I develop a view of what has gone wrong scientif cally and ask what can be done to address this parlous situation. Fig. 1. Terrible thing to waste. Pharma has removed psychiatric diseases from its body of drug discovery projects. Geneticists might help reverse the trend. [The Pilgrim by René Magritte. 1966]

show abstract

“…corticocortical connectivity | human transcriptome | association cortex | supragranular | brain evolution P atterns of gene expression in the cerebral cortex are generally conserved across species, reflecting strong constraints in the development and evolution of cortical architecture (1)(2)(3)(4)(5)(6). Previous work examining transcriptional variation in nonhuman primates and rodents indicate that molecular similarities between cortical regions in the adult brain are best explained by spatial proximity (7,8).…”

mentioning

confidence: 99%

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

Krienen

Yeo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

214

203

View full text Add to dashboard Cite

The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute's human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections.corticocortical connectivity | human transcriptome | association cortex | supragranular | brain evolution P atterns of gene expression in the cerebral cortex are generally conserved across species, reflecting strong constraints in the development and evolution of cortical architecture (1-6). Previous work examining transcriptional variation in nonhuman primates and rodents indicate that molecular similarities between cortical regions in the adult brain are best explained by spatial proximity (7, 8). Molecular variation often takes the form of graded expression along a principal axis, in many cases appearing as rostrocaudal gradients across the cortex (8). The strong tendency for transcriptional variation to follow spatial proximity in the adult cortex likely reflects both functional gradients, as well as their developmental origins in terms of physical and temporal adjacency during neurogenesis of cells destined for neighboring locations in the cortex (at least for cells derived from the ventricular proliferative pool) (7).Spatial proximity likely captures the major features governing how molecular profiles vary across the cortex in all species, including humans. However, the expansion of the cerebral cortex in primates...

show abstract

Human-Specific Transcriptional Networks in the Brain

Cited by 238 publications

References 87 publications

On the functions, mechanisms, and malfunctions of intracortical contextual modulation

On the functions, mechanisms, and malfunctions of intracortical contextual modulation

Revolution Stalled

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

Contact Info

Product

Resources

About