Endocannabinoid-dependent formation of columnar axonal projection in the mouse cerebral cortex.

Columnar structure is one of the most fundamental morphological features of the cerebral cortex and is thought to be the basis of information processing in higher animals. Yet, how such a topographically precise structure is formed is largely unknown. Formation of columnar projection of layer 4 (L4) axons is preceded by thalamocortical formation, in which type 1 cannabinoid receptors (CB1R) play an important role in shaping barrel-specific targeted projection by operating spike timing-dependent plasticity during development (Itami , 36, 7039-7054 [2016]; Kimura & Itami, 39, 3784-3791 [2019]).

A Hypothetical Model Concerning How Spike-Timing-Dependent Plasticity Contributes to Neural Circuit Formation and Initiation of the Critical Period in Barrel Cortex.

Spike timing is an important factor in the modification of synaptic strength. Various forms of spike timing-dependent plasticity (STDP) occur in the brains of diverse species, from insects to humans. In unimodal STDP, only LTP or LTD occurs at the synapse, regardless of which neuron spikes first; the magnitude of potentiation or depression increases as the time between presynaptic and postsynaptic spikes decreases.

The α -adrenoceptor suppresses excitatory synaptic transmission to both excitatory and inhibitory neurons in layer 4 barrel cortex.

Key Points: The effects of noradrenaline on excitatory synaptic transmission to regular spiking (excitatory) cells as well as regular spiking non-pyramidal and fast spiking (both inhibitory) cells in cortical layer 4 were studied in thalamocortical slice preparations, focusing on vertical input from thalamus and layer 2/3 in the mouse barrel cortex. Excitatory synaptic responses were suppressed by noradrenaline. However, currents induced by iontophoretically applied glutamate were not suppressed.

Concurrently induced plasticity due to convergence of distinct forms of spike timing-dependent plasticity in the developing barrel cortex.

Spike timing-dependent plasticity (STDP) has been demonstrated in a variety of neural circuits. Recent studies reveal that it plays a fundamental role in the formation and remodeling of neuronal circuits. We show here an interaction of two distinct forms of STDP in the mouse barrel cortex causing concurrent, plastic changes, potentially a novel mechanism underlying network remodeling.

Developmental Switch in Spike Timing-Dependent Plasticity and Cannabinoid-Dependent Reorganization of the Thalamocortical Projection in the Barrel Cortex.

Unlabelled: The formation and refinement of thalamocortical axons (TCAs) is an activity-dependent process (Katz and Shatz, 1996), but its mechanism and nature of activity are elusive. We studied the role of spike timing-dependent plasticity (STDP) in TCA formation and refinement in mice. At birth (postnatal day 0, P0), TCAs invade the cortical plate, from which layers 4 (L4) and L2/3 differentiate at P3-P4.

Role of electrical activity in horizontal axon growth in the developing cortex: a time-lapse study using optogenetic stimulation.

During development, layer 2/3 neurons in the neocortex extend their axons horizontally, within the same layers, and stop growing at appropriate locations to form branches and synaptic connections. Firing and synaptic activity are thought to be involved in this process, but how neuronal activity regulates axonal growth is not clear. Here, we studied axonal growth of layer 2/3 neurons by exciting cell bodies or axonal processes in organotypic slice cultures of the rat cortex.

Developmental switch in spike timing-dependent plasticity at layers 4-2/3 in the rodent barrel cortex.

Sensory deprivation during the critical period induces long-lasting changes in cortical maps. In the rodent somatosensory cortex (S1), its precise initiation mechanism is not known, yet spike timing-dependent plasticity (STDP) at layer 4 (L4)-L2/3 synapses are thought to be crucial. Whisker stimulation causes "L4 followed by L2/3" cell firings, while acute single whisker deprivation suddenly reverses the sequential order in L4 and L2/3 neurons in the deprived column (Celikel et al.

Decorrelation of sensory-evoked neuronal responses in rat barrel cortex during postnatal development.

The ability to detect and discriminate sensory stimuli greatly improves with age. To better understand the neural basis of perceptual development, we studied the postnatal development of sensory responses in cortical neurons. Specifically, we analyzed neuronal responses to single-whisker deflections in the posteromedial barrel subfield (PMBSF) of the rat primary somatosensory cortex.

Ephrin-A5 and EphA5 interaction induces synaptogenesis during early hippocampal development.

Background: Synaptogenesis is a fundamental step in neuronal development. For spiny glutamatergic synapses in hippocampus and cortex, synaptogenesis involves adhesion of pre and postsynaptic membranes, delivery and anchorage of pre and postsynaptic structures including scaffolds such as PSD-95 and NMDA and AMPA receptors, which are glutamate-gated ion channels, as well as the morphological maturation of spines. Although electrical activity-dependent mechanisms are established regulators of these processes, the mechanisms that function during early development, prior to the onset of electrical activity, are unclear.

Fast activation of feedforward inhibitory neurons from thalamic input and its relevance to the regulation of spike sequences in the barrel cortex.

Thalamocortical afferents innervate both excitatory and inhibitory cells, the latter in turn producing disynaptic feedforward inhibition, thus creating fast excitation-inhibition sequences in the cortical cells. Since this inhibition is disynaptic, the time lag of the excitation-inhibition sequence could be approximately 2-3 ms, while it is often as short as only slightly above 1 ms; the mechanism and function of such fast IPSPs are not fully understood. Here we show that thalamic activation of inhibitory neurons precedes that of excitatory neurons, due to increased conduction velocity of thalamic axons innervating inhibitory cells.

Myelination and isochronicity in neural networks.

Our brain contains a multiplicity of neuronal networks. In many of these, information sent from presynaptic neurons travels through a variety of pathways of different distances, yet arrives at the postsynaptic cells at the same time. Such isochronicity is achieved either by changes in the conduction velocity of axons or by lengthening the axonal path to compensate for fast conduction.

Brain-derived neurotrophic factor regulates the maturation of layer 4 fast-spiking cells after the second postnatal week in the developing barrel cortex.

Brain-derived neurotrophic factor (BDNF) has been reported to play a critical role in modulating plasticity in developing sensory cortices. In the visual cortex, maturation of neuronal circuits involving GABAergic neurons has been shown to trigger a critical period. To date, several classes of GABAergic neurons are known, each of which are thought to play distinct functions.

Transiently higher release probability during critical period at thalamocortical synapses in the mouse barrel cortex: relevance to differential short-term plasticity of AMPA and NMDA EPSCs and possible involvement of silent synapses.

Thalamocortical connections undergo remarkable plasticity during the critical period and mounting evidence serves to demonstrate that the activation of silent synapses at postsynaptic sites is an important underlying mechanism in this process. However, relatively little is known about the nature of the presynaptic properties. In the present study, we examined the release probability (Pr) of thalamocortical synaptic terminals on a layer IV neuron in the developing mouse barrel cortex.

Brain-derived neurotrophic factor-dependent unmasking of "silent" synapses in the developing mouse barrel cortex.

Brain-derived neurotrophic factor (BDNF) is a critical modulator of central synaptic functions such as long-term potentiation in the hippocampal and visual cortex. Little is known, however, about its role in the development of excitatory glutamatergic synapses in vivo. We investigated the development of N-methyl-D-aspartate (NMDA) receptor (NMDAR)-only synapses (silent synapses) and found that silent synapses were prominent in acute thalamocortical brain slices from BDNF knockout mice even after the critical period.

Change of conduction velocity by regional myelination yields constant latency irrespective of distance between thalamus and cortex.

The widely spanning sensory cortex receives inputs from the disproportionately smaller nucleus of the thalamus, which results in a wide variety of travelling distance among thalamic afferents. Yet, latency from the thalamus to a cortical cell is remarkably constant across the cortex (typically, approximately 2 ms). Here, we found a mechanism that produces invariability of latency among thalamocortical afferents, irrespective of the variability of travelling distances.