Neurons of human cognition

Research focus

One of the most fundamental questions in neuroscience has been one on the origin of human intelligence. We assume that our mind functions through the activity of almost hundred billion neurons and their connections, and ultimately give rise to cognition. Given the astronomic number of neuronal connections, even the slightest changes in the speed of computation of individual neurons can translate into large differences in overall computational power of the brain. What makes human neurons special and how do they support human cognition? These questions are the main focus of my research.

My team uses a multi-disciplinary approach to link genes, neurons, cortical areas and cognition by combining multi-scale data from the same human subjects. To study the living human neurons and their genetic fingerprint we use brain tissue from neurosurgery that is removed in order to reach deeper-lying subcortical tumor or epilepsy focus. We link neuronal properties to cognitive function by using pre-surgical cognitive tests from these patients, and to brain network function and cortical structure from MRI and MEG measurements. Finally, we apply computational models to understand how the studied mechanisms contribute to fast computation in neurons.

We have shown that several neuronal properties that distinguish human neurons from those of rodents, also can explain differences in cognitive ability in human subjects. After measuring neuronal properties from individuals with different IQ scores, we showed that neurons from subjects with high IQ test scores have larger and more complex dendrites, and faster electrical properties, which enable neurons to process information faster. In the follow-up work we showed that these neuronal properties lead to microstructural reorganization of cortical layers. Especially upper layers are thicker in individuals with higher IQ and contain larger neurons with lower neuronal density. Furthermore, exactly these cellular properties – larger dendrites and faster action potential – go hand in hand with increased integrative role of this brain area within global brain network.

My next ambition is to mechanistically study how genes associated with intelligence act in neurons in the human brain to support intelligence using recently developed single-cell Patch-RNA-sequencing technique in living human neurons.

1. Human neocortical expansion involves glutamatergic neuron diversification.
Berg J, Sorensen S, Ting J, Miller JA, [U01 BICCN consortium (125 authors)], Goriounova NA, Mansvelder HD, Tamas G, Zeng H, Koch C, Lein ES.
Nature (2021). 598(7879):151-158. doi: 10.1038/s41586-021-03813-8.

2. Verbal and General IQ Associate with Supragranular Layer Thickness and Cell Properties of the Left Temporal Cortex.
Heyer DB, Wilbers R, Galakhova AA, Hartsema E, Braak S, Hunt S, Verhoog MB, Muijtjens ML, Mertens EJ, Idema S, Baayen JC, de Witt Hamer P, Klein M, McGraw M, Lein ES, de Kock CPJ, Mansvelder HD, Goriounova NA.
Cereb Cortex (2021). 25:bhab330. doi: 10.1093/cercor/bhab330.

3. Cellular Substrates of Functional Network Integration and Memory in Temporal Lobe Epilepsy.
Douw L, Nissen IA, Fitzsimmons SMDD, Santos FAN, Hillebrand A, van Straaten ECW, Stam CJ, De Witt Hamer PC, Baayen JC, Klein M, Reijneveld JC, Heyer DB, Verhoog MB, Wilbers R, Hunt S, Mansvelder HD, Geurts JJG, de Kock CPJ, Goriounova NA.
Cereb Cortex (2021). 25:bhab349. doi: 10.1093/cercor/bhab349.

4. A community-based transcriptomics classification and nomenclature of neocortical cell types.
Yuste R, Hawrylycz M, …, Goriounova NA, …, Lein E.
Nature Neuroscience (2020). 23(12):1456-1468. doi: 10.1038/s41593-020-0685-8.

5. Genes, Cells and Brain Areas of Intelligence.
Goriounova NA, Mansvelder HD.
Front Hum Neurosci (2019). 13:44. doi: 10.3389/fnhum.2019.00044. eCollection 2019. doi: 10.3389/fnhum.2019.00044.

6. Synaptic plasticity in human cortical circuits: cellular mechanisms of learning and memory in the human brain?
Mansvelder HD, Verhoog MB, Goriounova NA.
Curr Opin Neurobiol (2019). 54:186-193.
doi: 10.1016/j.conb.2018.06.013.

7. Large and fast human pyramidal neurons associate with intelligence.
Goriounova NA, Heyer DB, Wilbers R, Verhoog MB, Giugliano M, Verbist C, Obermayer J, Kerkhofs A, Smeding H, Verberne M, Idema S, Baayen JC, Pieneman AW, de Kock CP, Klein M, Mansvelder HD.
Elife. 2018. 18;7:e41714. doi: 10.7554/eLife.41714.

8. Mechanisms underlying the rules for associative plasticity at adult human neocortical synapses.
Verhoog MB*, Goriounova NA*, Obermayer J, Stroeder J, Hjorth JJ, Testa-Silva G, Baayen JC, de Kock CP,
Meredith RM, Mansvelder HD.
Journal of Neuroscience (2013) 23;33(43):17197-208. doi: 10.1523/JNEUROSCI.3158-13.2013.
*equal contribution

9. Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence.
Counotte DS*, Goriounova NA*, Li KW, Loos M, van der Schors RC, Schetters D, Schoffelmeer AN, Smit AB, Mansvelder HD, Pattij T, Spijker S.
Nature Neuroscience (2011). 14(4):417-9. doi: 10.1038/nn.2770.
*equal contribution

10. Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release.
Groffen AJ, Martens S, Díez Arazola R, Cornelisse LN, Lozovaya N, de Jong AP, Goriounova NA, Habets RL, Takai Y, Borst JG, Brose N, McMahon HT, Verhage M.
Science (2010). 327 (5973), 1614-1618.

11. Prefrontal cortex AMPA receptor plasticity is crucial for cue-induced relapse to heroin-seeking.
Van den Oever MC, Goriounova NA, Li KW, Van der Schors RC, Binnekade R, Schoffelmeer AN, Mansvelder HD, Smit AB, De Vries TJ, Spijker S.
Nature Neuroscience (2008). 11 (9), 1053-1058.