Genes, Cells and Brain Areas of Intelligence

What is the neurobiological basis of human intelligence? The brains of some people seem to be more efficient than those of others. Understanding the biological foundations of these differences is of great interest to basic and applied neuroscience. Somehow, the secret must lie in the cells in our brain with which we think. However, at present, research into the neurobiology of intelligence is divided between two main strategies: brain imaging studies investigate macroscopic brain structure and function to identify brain areas involved in intelligence, while genetic associations studies aim to pinpoint genes and genetic loci associated with intelligence. Nothing is known about how properties of brain cells relate to intelligence. The emergence of transcriptomics and cellular neuroscience of intelligence might, however, provide a third strategy and bridge the gap between identified genes for intelligence and brain function and structure. Here, we discuss the latest developments in the search for the biological basis of intelligence. In particular, the recent availability of very large cohorts with hundreds of thousands of individuals have propelled exciting developments in the genetics of intelligence. Furthermore, we discuss the first studies that show that specific populations of brain cells associate with intelligence. Finally, we highlight how specific genes that have been identified generate cellular properties associated with intelligence and may ultimately explain structure and function of the brain areas involved. Thereby, the road is paved for a cellular understanding of intelligence, which will provide a conceptual scaffold for understanding how the constellation of identified genes benefit cellular functions that support intelligence

Human Synapses Show a Wide Temporal Window for Spike-Timing-Dependent Plasticity

Throughout our lifetime, activity-dependent changes in neuronal connection strength enable the brain to refine neural circuits and learn based on experience. Synapses can bi-directionally alter strength and the magnitude and sign depend on the millisecond timing of presynaptic and postsynaptic action potential firing. Recent findings on laboratory animals have shown that neurons can show a variety of temporal windows for spike-timing-dependent plasticity (STDP). It is unknown what synaptic learning rules exist in human synapses and whether similar temporal windows for STDP at synapses hold true for the human brain. Here, we directly tested in human slices cut from hippocampal tissue removed for surgical treatment of deeper brain structures in drug-resistant epilepsy patients, whether adult human synapses can change strength in response to millisecond timing of pre- and postsynaptic firing. We find that adult human hippocampal synapses can alter synapse strength in response to timed pre- and postsynaptic activity. In contrast to rodent hippocampal synapses, the sign of plasticity does not sharply switch around 0-ms timing. Instead, both positive timing intervals, in which presynaptic firing preceded the postsynaptic action potential, and negative timing intervals, in which postsynaptic firing preceded presynaptic activity down to −80 ms, increase synapse strength (tLTP). Negative timing intervals between −80 to −130 ms induce a lasting reduction of synapse strength (tLTD). Thus, similar to rodent synapses, adult human synapses can show spike-timing-dependent changes in strength. The timing rules of STDP in human hippocampus, however, seem to differ from rodent hippocampus, and suggest a less strict interpretation of Hebb's predictions

Synaptic plasticity in human cortical circuits: cellular mechanisms of learning and memory in the human brain?

Synaptic plasticity is the cellular basis of learning and memory, but to what extent this holds for the adult human brain is not known. To study synaptic plasticity in human neuronal circuits poses a huge challenge, since live human neurons and synapses are not readily accessible. Despite this, various lines of research have provided insights in properties of adult human synapses and their plasticity both in vitro and in vivo, with some unexpected surprises. We first discuss the experimental approaches to study activity-dependent plasticity of adult human synapses, and then highlight rules and mechanisms of Hebbian spike timing-dependent plasticity (STDP) found in these synapses. Finally, we conclude with thoughts on how these synaptic principles can underlie human learning and memory

Lateral inhibition by Martinotti interneurons is facilitated by cholinergic inputs in human and mouse neocortex

Parvalbumin and somatostatin expressing interneurons mediate lateral inhibition between cortical neurons. Here the authors report the mechanisms by which acetylcholine from the basal forebrain selectively augments lateral inhibition via Martinotti cells and show that this is conserved in humans

Group I mGluR-mediated activation of martinotti cells inhibits local cortical circuitry in human cortex

Group I metabotropic glutamate receptors (mGluRs) mediate a range of signaling and plasticity processes in the brain and are of growing importance as potential therapeutic targets in clinical trials for neuropsychiatric and neurodevelopmental disorders (NDDs). Fundamental knowledge regarding the functional effects of mGluRs upon pyramidal neurons and interneurons is derived largely from rodent brain, and their effects upon human neurons are predominantly untested. We therefore addressed how group I mGluRs affect microcircuits in human neocortex. We show that activation of group I mGluRs elicits action potential firing in Martinotti cells, which leads to increased synaptic inhibition onto neighboring neurons. Some other interneurons, including fast-spiking interneurons, are depolarized but do not fire action potentials in response to group I mGluR activation. Furthermore, we confirm the existence of group I mGluR-mediated depression of excitatory synapses in human pyramidal neurons. We propose that the strong increase in inhibition and depression of excitatory synapses onto layer 2/3 pyramidal neurons upon group I mGluR activation likely results in a shift in the balance between excitation and inhibition in the human cortical network

Author Correction:Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention (Nature Communications, (2019), 10, 1, (5280), 10.1038/s41467-019-13244-9)

The original version of this Article contained an error in the spelling of the author Wilma D.J. van de Berg, which was incorrectly given as Wilma D.J. van den Berg. This has now been corrected in both the PDF and HTML versions of the Article