Cortical interneurons can be categorized into distinct populations based on multiple modalities, including molecular signatures and morpho-electrical (M/E) properties. Recently, many transcriptomic signatures based on single-cell RNA-seq have been identified in cortical interneurons. However, whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown. Here, we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA (mRNA) expression of >600 interneurons in layer V of the mouse somatosensory cortex (S1). Subsequently, we identified 11 M/E subtypes, 9 neurochemical cell populations (NCs), and 20 transcriptomic cell populations (TCs) in this cortical lamina. Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically. A similar analysis of layer V interneurons of mouse primary visual cortex (V1) and motor cortex (M1) gave results largely comparable to S1. Comparison between S1, V1, and M1 suggested that, compared to V1, S1 interneurons were morpho-electrically more similar to M1. Our study reveals the presence of substantial M/E variations in cortical interneuron populations defined by molecular expression.
Mice ; Animals ; Neocortex/physiology* ; Mice, Transgenic ; Interneurons/physiology*

AIMTo study the role of the caudate-putamen (CPu)-hippocampus (HPC)-medial temporal lobe neocortex (MTNC) neural pathway in re-establishment of pathophysiological neural networks related to epileptogenesis.

METHODSExperiments were performed under anaesthesia on 45 SD rats. The right HPC, the right MTNC, bilateral HPC, the right HPC and the right MTNC depth electrographs were recorded with bipolar concentric electrodes. Tetanization (60 Hz, 2 s, 0.4 - 0.6 mA) of the right CPu or of the right HPC trains were used to establish acute rat epilepsy model. These depth electrographs were detected before or after tetani were delivered about 10 times at 10 min intervals.

RESULTSTetanization of the right CPu induced (1) primary afterdischarges and unilateral or bilateral HPC electrographic afterdischarges and kindling effect or inhibition-rebound-kindling effect were induced by repetitive tetani into the right CPu. (2) After injection of scopolamine (0.05 mg/kg i.p.), 3 Hz slow oscillations in HPC electrographs exhibited long-term potentiation followed by repetitive tetani into the right CPu. (3) After administration of scopolamine (i.p.) electrographic oscillations at 3Hz with synaptic modification in bilateral HPC were induced and epileptiform activities in the RHPC were synchronized with those in the RMTNC.

CONCLUSIONPathophysiological neural networks from the Cpu into the HPC might be reestablished by overactivation of the right CPu, in which two hemispheres are involved while temporal lobe epileptogenesis was facilitated.

Animals ; Caudate Nucleus ; physiology ; Electric Stimulation ; Hippocampus ; physiology ; Male ; Neocortex ; physiology ; Neural Pathways ; Putamen ; physiology ; Rats ; Rats, Sprague-Dawley ; Temporal Lobe ; physiology

A new method of axon recording through axon bleb has boosted the studies on the functional role of central nervous system (CNS) axons. Using this method, we have revealed the mechanisms underlying the initiation and propagation of the digital-mode signal, all-or-none action potentials (APs), in neocortical pyramidal neurons. Accumulation of the low-threshold Na(+) channel subtype Na(v)1.6 at the distal end of the axon initial segment (AIS) determines the lowest threshold for AP initiation, whereas accumulation of the high-threshold subtype Na(v)1.2 at the proximal region of the AIS promotes AP backpropagation to the soma and dendrites. Through dual recording from the soma and the axon, we have showed that subthreshold membrane potential (V(m)) fluctuations in the soma propagate along the axon to a long distance and probably reach the axon terminals. Paired recording from cortical neurons has revealed that these V(m) changes in the soma modulate AP-triggered synaptic transmission. This new V(m)-dependent mode of synaptic transmission is called analog communication. Unique properties of axonal K(+) channels (K(v)1 channels) may contribute to shaping the AP waveform, particularly its duration, and thus controlling synaptic strength at different levels of presynaptic V(m). The level of background Ca(2+) may also participate in mediating the analog signaling. Together, these findings enrich our knowledge on the principles of neuronal signaling in the CNS and help understand how the brain works.
Action Potentials ; physiology ; Animals ; Axons ; physiology ; Central Nervous System ; cytology ; physiology ; Humans ; Membrane Potentials ; physiology ; NAV1.2 Voltage-Gated Sodium Channel ; physiology ; NAV1.6 Voltage-Gated Sodium Channel ; physiology ; Neocortex ; cytology ; physiology ; Patch-Clamp Techniques ; Pyramidal Cells ; physiology ; Sodium Channels ; physiology

AIMTo investigat the effects of donepezil on delayed rectifier-like potassium currents (IK) in rat hippocampus and neocortex.

METHODSWhole cell configuration of the patch-clamp techniques were used to characterize IK in acutely isolated rat hippocampal and neocortical pyramidal neurons.

RESULTSThe slowly inactivating outward currents (IK) were recorded in all cells under investigation. Donepezil in micromolar concentrations were shown to supress the IK of all cells in a dose-dependent and voltage-dependent manner. The steady-state activation curves of IK were characterized by half-activation potentials of -15.5 mV in hippocampal and -4.1 mV in neocortical pyramidal neurons and were changed to -26.2 mV and -18.6 mV, respectively, after perfusion with donepezil (10 mumol.L-1).

CONCLUSIONAt concentrations as low as 1 mumol.L-1, donepezil was found to block the IK in a voltage-dependent manner in hippocampus and neocortex. This effect may be synergistic with the anticholinesterase activity of donepezil to increase its therapeutic effectiveness.

Animals ; Cholinesterase Inhibitors ; pharmacology ; Delayed Rectifier Potassium Channels ; Hippocampus ; cytology ; In Vitro Techniques ; Indans ; pharmacology ; Male ; Neocortex ; cytology ; Neurons ; drug effects ; metabolism ; Patch-Clamp Techniques ; Piperidines ; pharmacology ; Potassium Channels ; drug effects ; physiology ; Potassium Channels, Voltage-Gated ; Pyramidal Cells ; drug effects ; metabolism ; Rats ; Rats, Wistar

The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.
Action Potentials ; physiology ; Biomarkers ; metabolism ; Cell Culture Techniques ; Embryoid Bodies ; cytology ; metabolism ; Gene Expression ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Lateral Ventricles ; cytology ; growth & development ; metabolism ; Microcephaly ; genetics ; metabolism ; pathology ; Models, Biological ; Mutation ; Neocortex ; cytology ; growth & development ; metabolism ; Nerve Tissue Proteins ; deficiency ; genetics ; Neurogenesis ; genetics ; Neurons ; cytology ; metabolism ; Organoids ; cytology ; metabolism ; PAX6 Transcription Factor ; genetics ; metabolism ; Patch-Clamp Techniques ; SOXB1 Transcription Factors ; genetics ; metabolism ; Zonula Occludens-1 Protein ; genetics ; metabolism