Dendrites of Neocortical Pyramidal Neurons: The Key to Understand Intellectual Disability

Pyramidal neurons (PNs) are the most abundant cells of the neocortex and display a vast dendritic tree, divided into basal and apical compartments. Morphological and functional anomalies of PN dendrites are at the basis of virtually all neurological and mental disorders, including intellectual disability. Here, we provide evidence that the cognitive deficits observed in different types of intellectual disability might be sustained by different parts of the PN dendritic tree, or by a dysregulation of their interaction.

Dendrites of Neocortical Pyramidal Neurons: The Key to Understand Intellectual Disability

Pyramidal neurons (PNs) are the most abundant cells of the neocortex and display a vast dendritic tree, divided into basal and apical compartments. Morphological and functional anomalies of PN dendrites are at the basis of virtually all neurological and mental disorders, including intellectual disability. Here we provide evidence that the cognitive deficits observed in different types of intellectual disability might be sustained by different parts of the PN dendritic tree, or by a dysregulation of their interaction.

Ciliary neuropeptidergic signaling dynamically regulates excitatory synapses in postnatal neocortical pyramidal neurons

Primary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured rat neocortical pyramidal neurons and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to excitatory neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies.

Ciliary neuropeptidergic signaling dynamically regulates excitatory synapses in postnatal neocortical pyramidal neurons

ABSTRACTPrimary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured neocortical pyramidal neurons, and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to pyramidal neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses, and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies.