bioRxiv Science⌕ Search

Biology subjects

Bayazitov, I. T.

Publications and source records attributed to Bayazitov, I. T..

2 recordsLinked to original sources

Neuronal primary cilia are not required for hippocampal circuit function or behavior in adult mice

Primary cilia, which are present in most brain cells, are essential for brain development and function. During early brain development, dysfunction of the primary cilia can lead to a broad spectrum of disorders, collectively termed ciliopathies, that include brain malformations and intellectual disability. Although the role of primary cilia in brain development is well-established, cilia-mediated signaling in mature neurons and the contribution of cilia to neuronal circuit function remain controversial. Using mouse genetic and behavioral studies, single-cell electrophysiology, and 2-photon imaging, we show that deletion of primary cilia from adult hippocampal neurons is not required for hippocampal circuit function or behavior. Chronic genetic deletion or acute laser ablation of primary cilia from mature pyramidal neurons in the CA1 or CA3 regions of the hippocampus did not affect neuronal excitability, basal synaptic transmission, or long-term synaptic plasticity at excitatory CA3-CA1 hippocampal synapses. Moreover, the loss of primary cilia did not affect hippocampal-dependent learning and memory or anxiety-like behaviors. These results challenge the prevailing view of cilia function in mature hippocampal neurons and suggest that neuronal cilia in the adult hippocampus do not serve as major signaling hubs for pathways essential for neuronal function or behavior.

neuroscience↗

Synaptic plasticity in human thalamocortical assembloids

Synaptic plasticities, such as long-term potentiation (LTP) and depression (LTD), tune synaptic efficacy and are essential for learning and memory. Current studies of synaptic plasticity in humans are limited by a lack of adequate human models. Here, we modeled the thalamocortical system by fusing human induced pluripotent stem cell-derived thalamic and cortical organoids. Single-nucleus RNA-sequencing revealed that most cells in mature thalamic organoids were glutamatergic neurons. When fused to form thalamocortical assembloids, thalamic and cortical organoids formed reciprocal long-range axonal projections and reciprocal synapses detectable by light and electron microscopy, respectively. Using whole-cell patch-clamp electrophysiology and two-photon imaging, we characterized glutamatergic synaptic transmission. Thalamocortical and corticothalamic synapses displayed short-term plasticity analogous to that in animal models. LTP and LTD were reliably induced at both synapses; however, their mechanisms differed from those previously described in rodents. Thus, thalamocortical assembloids provide a model system for exploring synaptic plasticity in human circuits. HighlightsO_LIHuman thalamic organoids consist of mostly glutamatergic projection neurons. C_LIO_LIThalamocortical assembloids form reciprocal glutamatergic synapses. C_LIO_LISynapses are functional and undergo short-term plasticity resembling animal models. C_LIO_LILong-term potentiation and depression reveal mechanisms distinct from rodents. C_LI eTOCHuman organoids are often used to model diseases with synaptic pathology; however, few studies have examined synaptic function via single-cell or single-synapse recordings. Patton et al. fused human thalamic and cortical organoids into assembloids to examine synaptic transmission and short- and long-term synaptic plasticity in human thalamocortical and corticothalamic circuits. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=199 HEIGHT=200 SRC="FIGDIR/small/578421v2_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@21546org.highwire.dtl.DTLVardef@c2ba28org.highwire.dtl.DTLVardef@4bc28aorg.highwire.dtl.DTLVardef@1d12a98_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗