Excitatory projection neuron subtypes control the distribution of local inhibitory interneurons in the cerebral cortex

In the mammalian cerebral cortex, the developmental events governing the integration of excitatory projection neurons and inhibitory interneurons into balanced local circuitry are poorly understood. We report that different subtypes of projection neurons uniquely and differentially determine the laminar distribution of cortical interneurons. We find that in Fezf2?/? cortex, the exclusive absence of subcerebral projection neurons and their replacement by callosal projection neurons cause distinctly abnormal lamination of interneurons and altered GABAergic inhibition. In addition, experimental generation of either corticofugal neurons or callosal neurons below the cortex is sufficient to recruit cortical interneurons to these ectopic locations. Strikingly, the identity of the projection neurons generated, rather than strictly their birthdate, determines the specific types of interneurons recruited. These data demonstrate that in the neocortex individual populations of projection neurons cell-extrinsically control the laminar fate of interneurons and the assembly of local inhibitory circuitry.     

Keeping inhibition timely

GABAergic interneurons play a key role in orchestrating cortical network oscillations. In this issue of Neuron, two studies (Bacci and Huguenard and Vida et al.) identify how networks of fast-spiking interneurons can enhance the regularity, precision, and robustness of their own rhythmicity via individual and collective self-innervation.     

Martinotti cells: community organizers

The specificity of connections made by inhibitory interneurons in the neocortex is not well understood. In this issue of Neuron, Fino and Yuste (2011) use an enhanced version of two-photon glutamate uncaging, which preserves inhibitory synaptic transmission, to demonstrate that somatostatin-positive interneurons form densely convergent connections onto pyramidal cells in layer 2/3 of mouse frontal cortex.     

CXCR4 and CXCR7 have distinct functions in regulating interneuron migration

CXCL12/CXCR4 signaling is critical for cortical interneuron migration and their final laminar distribution. No information is yet available on CXCR7, a newly defined CXCL12 receptor. Here we demonstrated that CXCR7 regulated interneuron migration autonomously, as well as nonautonomously through its expression in immature projection neurons. Migrating cortical interneurons coexpressed Cxcr4 and Cxcr7, and Cxcr7(-/-) and Cxcr4(-/-) mutants had similar defects in interneuron positioning. Ectopic CXCL12 expression and pharmacological blockade of CXCR4 in Cxcr7(-/-) mutants showed that both receptors were essential for responding to CXCL12 during interneuron migration. Furthermore, live imaging revealed that Cxcr4(-/-) and Cxcr7(-/-) mutants had opposite defects in interneuron motility and leading process morphology. In?vivo inhibition of Gα(i/o) signaling in migrating interneurons phenocopied the interneuron lamination defects of Cxcr4(-/-) mutants. On the other hand, CXCL12 stimulation of CXCR7, but not CXCR4, promoted MAP kinase signaling. Thus, we suggest that CXCR4 and CXCR7 have distinct roles and signal transduction in regulating interneuron movement and laminar positioning.     

Probing the locomotor conundrum: descending the 'V' interneuron ladder

The assembly of neuronal circuits involved in locomotor control in the mammalian spinal cord is influenced by genetic programs specifying four ventral (V) interneuron populations (V0-V3). In this issue of Neuron, Crone et al. and Zhang et al. make use of genetic tools to map connectivity patterns and to abolish the function of V2a and V3 interneurons. The absence of V2a interneurons reveals defects in left-right alternation during locomotion, whereas ablation of either V2a or V3 interneurons leads to disturbances in the precision and reliability of the motor output.     

The following article for this Special Issue was previously published and can be found in its respective issue online: “Acetylcholine release from striatal cholinergic interneurons is controlled differently depending on the firing pattern”

Acetylcholine release from striatal cholinergic interneurons is controlled differently depending on the firing pattern (Published in JNC 167.1 issue) https://onlinelibrary.wiley.com/doi/10.1111/jnc.15950     

Neurons on the move: migration and lamination of cortical interneurons

The modulation of cortical activity by GABAergic interneurons is required for normal brain function and is achieved through the immense level of heterogeneity within this neuronal population. Cortical interneurons share a common origin in the ventral telencephalon, yet during the maturation process diverse subtypes are generated that form the characteristic laminar arrangement observed in the adult brain. The long distance tangential and short-range radial migration into the cortical plate is regulated by a combination of intrinsic and extrinsic signalling mechanisms, and a great deal of progress has been made to understand these developmental events. In this review, we will summarize current findings regarding the molecular control of subtype specification and provide a detailed account of the migratory cues influencing interneuron migration and lamination. Furthermore, a dysfunctional GABAergic system is associated with a number of neurological and psychiatric conditions, and some of these may have a developmental aetiology with alterations in interneuron generation and migration. We will discuss the notion of additional sources of interneuron progenitors found in human and non-human primates and illustrate how the disruption of early developmental events can instigate a loss in GABAergic function.     

Retinoblastoma teaches a new lesson

In this issue, Ajioka et al. (2007) report a new mouse model of retinoblastoma. They show that retinoblastoma is not driven by uncontrolled expansion of retinal progenitor cells, but rather is the result of cell cycle re-entry and expansion of differentiated horizontal interneurons in the retina.     

Patterning spinal motor activity in the absence of synaptic excitation

Alternate activation of antagonistic muscles across a joint is essential for movement. A new study, by Talpalar et?al., in this issue of Neuron highlights the importance of spinal cord inhibitory interneurons in generating motor activity by showing that they can generate alternating flexor-extensor motor neuron firing in the absence of glutamatergic synaptic input.     

Differential susceptibility of interneurons expressing neuropeptide Y or parvalbumin in the aged hippocampus to acute seizure activity

Acute seizure (AS) activity in old age has an increased predisposition for evolving into temporal lobe epilepsy (TLE). Furthermore, spontaneous seizures and cognitive dysfunction after AS activity are often intense in the aged population than in young adults. This could be due to an increased vulnerability of inhibitory interneurons in the aged hippocampus to AS activity. We investigated this issue by comparing the survival of hippocampal GABA-ergic interneurons that contain the neuropeptide Y (NPY) or the calcium binding protein parvalbumin (PV) between young adult (5-months old) and aged (22-months old) F344 rats at 12 days after three-hours of AS activity. Graded intraperitoneal injections of the kainic acid (KA) induced AS activity and a diazepam injection at 3 hours after the onset terminated AS-activity. Measurement of interneuron numbers in different hippocampal subfields revealed that NPY+ interneurons were relatively resistant to AS activity in the aged hippocampus in comparison to the young adult hippocampus. Whereas, PV+ interneurons were highly susceptible to AS activity in both age groups. However, as aging alone substantially depleted these populations, the aged hippocampus after three-hours of AS activity exhibited 48% reductions in NPY+ interneurons and 70% reductions in PV+ interneurons, in comparison to the young hippocampus after similar AS activity. Thus, AS activity-induced TLE in old age is associated with far fewer hippocampal NPY+ and PV+ interneuron numbers than AS-induced TLE in the young adult age. This discrepancy likely underlies the severe spontaneous seizures and cognitive dysfunction observed in the aged people after AS activity.     

A novel local circuit in the olfactory bulb involving an old short-axon cell

Many local circuit interactions in the olfactory bulb involve atypical dendrodendritic synapses. In this issue of Neuron, Pressler and Strowbridge report a functional analysis of a class of short-axon interneurons in the bulb called Blanes cells. Blanes cells make GABAergic axonal contacts onto granule cells and may mediate a form of local feedforward disinhibition.     

Local peptidergic signaling in the antennal lobe shapes olfactory behavior

Transfer and processing of olfactory information in the antennal lobe of Drosophila relies primarily on neurotransmitters such as acetylcholine and GABA, but novel studies also implicated a neuropeptide: the Drosophila tachykinin (DTK). DTK is expressed in local interneurons that innervate the glomeruli of the antennal lobe with varicose processes. Recently, DTK was shown to mediate presynaptic inhibition of olfactory sensory neurons by physiological and behavioral analysis (Ignell et al. 2009, PNAS). That study drew our attention to the issue of alternative targets of DTK in the antennal lobe. Hence, in the present study, we interfered with DTK peptide and DTK receptor (DTKR) expression in local interneurons of the antennal lobe and studied the behavioral outcome of these manipulations. We show that the DTKR is expressed not only in olfactory sensory neurons, but most likely also in local interneurons. The behavioral consequences of interfering with postsynaptic peptide receptors are different from presynaptic peptide receptor interference. We discuss the possibility that the sum of pre- and postsynaptic interactions may be to modulate the dynamic range in odor sensitivity.     

γ节律振荡机制在视觉研究中的新进展

γ节律振荡是大脑皮质中常见的,频率在30～80 Hz之间的神经振荡模式,在初级视觉通道中能观察到多种起源的γ节律振荡.在小鼠、猫与猴V1的视觉诱发的γ节律振荡主要起源于L2/3和L4B,并对刺激参数敏感.猫与小鼠初级视觉通道(视网膜、LGN与V1)中观察到起源于视网膜由亮度诱发的高频γ节律振荡;在猴LGN却没有观察到γ节律振荡,而在V1上记录到亮度诱发的γ活动.γ节律振荡的产生与抑制性中间神经元网络有重要的关系,其中抑制性中间神经元中PV细胞被认为与自发γ节律振荡的产生相关. SOM细胞的参与对低频γ节律振荡(20～40 Hz)的产生起到关键作用;而光栅诱发的高频γ节律振荡(65～80 Hz)主要与PV细胞有关.动物在不同生理状态、发育阶段与脑疾病状态下光栅诱发的γ节律振荡存在较大差异,反映大脑对视觉信息加工的变化.     

Time to change: retina sends a messenger to promote plasticity in visual cortex

Maturation of GABA inhibitory circuitry in primary visual cortex activates the critical period of plasticity, but the underlying mechanisms are not well understood. In the August 8th issue of Cell, Sugiyama et al. demonstrate that visual experience promotes the passage of a retina-derived homeoprotein along the visual pathway, which nurtures subclasses of cortical interneurons implicated in regulating critical period plasticity.     

Otx2's incredible journey

A surprising new mechanism that regulates the plasticity of postnatal neurons is reported in this issue by Sugiyama et al. (2008). These authors show in mice that visual experience triggers cell-to-cell transfer of the homeoprotein Otx2 to cortical interneurons, where it promotes maturation of inhibitory neural circuitry and opens the critical period for plasticity in the visual cortex.     

Multiple mechanisms for contrast adaptation in the retina

The retina adapts to average light intensity but also to the range of light intensities (contrast). A study by Baccus and Meister, in this issue of Neuron, identifies three ways that ganglion cells and interneurons adapt to high contrast: shorten integration time, reduce gain, and depolarize. Only the depolarization decays, over tens of seconds.     

Disentanglement of local field potential sources by independent component analysis

The spontaneous activity of working neurons yields synaptic currents that mix up in the volume conductor. This activity is picked up by intracerebral recording electrodes as local field potentials (LFPs), but their separation into original informative sources is an unresolved problem. Assuming that synaptic currents have stationary placing we implemented independent component model for blind source separation of LFPs in the hippocampal CA1 region. After suppressing contaminating sources from adjacent regions we obtained three main local LFP generators. The specificity of the information contained in isolated generators is much higher than in raw potentials as revealed by stronger phase-spike correlation with local putative interneurons. The spatial distribution of the population synaptic input corresponding to each isolated generator was disclosed by current-source density analysis of spatial weights. The found generators match with axonal terminal fields from subtypes of local interneurons and associational fibers from nearby subfields. The found distributions of synaptic currents were employed in a computational model to reconstruct spontaneous LFPs. The phase-spike correlations of simulated units and LFPs show laminar dependency that reflects the nature and magnitude of the synaptic currents in the targeted pyramidal cells. We propose that each isolated generator captures the synaptic activity driven by a different neuron subpopulation. This offers experimentally justified model of local circuits creating extracellular potential, which involves distinct neuron subtypes.