Postnatal connectomic development of inhibition in mouse barrel cortex

Brain circuits in the neocortex develop from diverse types of neurons that migrate and form synapses. Here we quantify the circuit patterns of synaptogenesis for inhibitory interneurons in the developing mouse somatosensory cortex. We studied synaptic innervation of cell bodies, apical dendrites and axon initial segments using 3D electron microscopy focusing on the first four weeks postnatally (postnatal days 5 to 28). We found that innervation of apical dendrites occurs early and specifically: target preference is already almost at adult levels at the fifth postnatal day (P5). Axons innervating cell bodies, on the other hand, gradually acquire specificity from P5 to P9 likely via synaptic overabundance followed by antispecific synapse removal. Chandelier axons show first target preference by P14 but develop full target specificity almost completely by P28, consistent with a combination of axon outgrowth and off-target synapse removal. This connectomic developmental profile reveals how inhibitory axons in mouse cortex establish brain circuitry during development.

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Two Dynamically Distinct Inhibitory Networks in Layer 4 of the Neocortex

Journal of Neurophysiology ◽

10.1152/jn.00283.2003 ◽

2003 ◽

Vol 90 (5) ◽

pp. 2987-3000 ◽

Cited By ~ 343

Author(s):

Michael Beierlein ◽

Jay R. Gibson ◽

Barry W. Connors

Keyword(s):

Barrel Cortex ◽

Dynamic Properties ◽

Inhibitory Synapses ◽

Projection Neurons ◽

Inhibitory Interneurons ◽

Short Term ◽

Layer 4 ◽

Recurrent Collaterals ◽

Chemical Synapses ◽

Excitatory And Inhibitory Synapses

Normal operations of the neocortex depend critically on several types of inhibitory interneurons, but the specific function of each type is unknown. One possibility is that interneurons are differentially engaged by patterns of activity that vary in frequency and timing. To explore this, we studied the strength and short-term dynamics of chemical synapses interconnecting local excitatory neurons (regular-spiking, or RS, cells) with two types of inhibitory interneurons: fast-spiking (FS) cells, and low-threshold spiking (LTS) cells of layer 4 in the rat barrel cortex. We also tested two other pathways onto the interneurons: thalamocortical connections and recurrent collaterals from corticothalamic projection neurons of layer 6. The excitatory and inhibitory synapses interconnecting RS cells and FS cells were highly reliable in response to single stimuli and displayed strong short-term depression. In contrast, excitatory and inhibitory synapses interconnecting the RS and LTS cells were less reliable when initially activated. Excitatory synapses from RS cells onto LTS cells showed dramatic short-term facilitation, whereas inhibitory synapses made by LTS cells onto RS cells facilitated modestly or slightly depressed. Thalamocortical inputs strongly excited both RS and FS cells but rarely and only weakly contacted LTS cells. Both types of interneurons were strongly excited by facilitating synapses from axon collaterals of corticothalamic neurons. We conclude that there are two parallel but dynamically distinct systems of synaptic inhibition in layer 4 of neocortex, each defined by its intrinsic spiking properties, the short-term plasticity of its chemical synapses, and (as shown previously) an exclusive set of electrical synapses. Because of their unique dynamic properties, each inhibitory network will be recruited by different temporal patterns of cortical activity.

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A lifespan program of mouse synaptome architecture

10.1101/838458 ◽

2019 ◽

Author(s):

Mélissa Cizeron ◽

Zhen Qiu ◽

Babis Koniaris ◽

Ragini Gokhale ◽

Noboru H. Komiyama ◽

...

Keyword(s):

Young Adults ◽

Old Age ◽

Mouse Brain ◽

Protein Composition ◽

Brain Regions ◽

Intellectual Ability ◽

Brain Circuits ◽

Brain Circuitry ◽

Wide Scale ◽

The Brain

AbstractHow synapses change molecularly during the lifespan and across all brain circuits is unknown. We analyzed the protein composition of billions of individual synapses from birth to old age on a brain-wide scale in the mouse, revealing a program of changes in the lifespan synaptome architecture spanning individual dendrites to the systems level. Three major phases were uncovered, corresponding to human childhood, adulthood and old age. An arching trajectory of synaptome architecture drives the differentiation and specialization of brain regions to a peak in young adults before dedifferentiation returns the brain to a juvenile state. This trajectory underscores changing network organization and hippocampal physiology that may account for lifespan transitions in intellectual ability and memory, and the onset of behavioral disorders.One sentence summaryThe synaptome architecture of the mouse brain undergoes continuous changes that organize brain circuitry across the lifespan.

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Somatosensory Crossmodal Plasticity in Superior Colliculus of Visually Deafferented Rats

Medical Research Archives ◽

10.18103/mra.v9i5.2432 ◽

2021 ◽

Vol 9 (5) ◽

Author(s):

Luis Millan ◽

Juan Charaven

Keyword(s):

Visual Cortex ◽

Superior Colliculus ◽

Barrel Cortex ◽

Young Animal ◽

Sensory Information ◽

The Other ◽

Reactive Synaptogenesis ◽

Somatosensory Information ◽

Crossmodal Plasticity ◽

Visual Afferents

Terminal fields of a certain pathway result denervated if the regeneration after the lesion of the pathway fails. If the lesion happened in a young animal, terminal fields of other nervous pathways that are spatially coincident or are close to the denervated field, growth of axon collaterals or reactive synaptogenesis could take place and reinervate deafferented neurons. In that way these denervated neurons can be recruited for functional compensatory responses and can convey information to areas that result enriched with additional inputs to be processed. The present paper reviews the plastic reactions that take place in the superior colliculus, a mesencephalic layered structure, after the neonatal suppression of its visual afferents that terminate in its superficial layers. The postlesional reactive ascending growth of somatosensory afferents that in control animals innervate intermediate and deep collicular layers invade the superficial layers and connect with visually deafferented cells that result recruited for descendent collicular responses and to send sensory information to the visual cortex via the colliculo-geniculate payhway. In that way in neonatally deafferented animals, somatosensory information gains additional territory to be processed. Two somatosensory connections to the superior collicuus will be discussed in this review. One ascending from the cuneitorm nucleus and the other descending that originates in the barrel cortex.

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Help or flight: Neural defensive circuits promote helping under threat in humans

10.1101/2021.12.17.473167 ◽

2021 ◽

Author(s):

Joana B Vieira ◽

Andreas Olsson

Keyword(s):

Neural Circuits ◽

The Other ◽

Similarity Analysis ◽

Representational Similarity Analysis ◽

Defensive Responses ◽

Helping Behaviour ◽

Brain Circuitry ◽

The Impact

Helping of conspecifics under threat has been observed across species. In humans, the dominant view proposes that empathy is the key proximal mechanism driving helping motivation in a threatening context, but little is known about how one s own defensive responses to the threat may guide helping decisions. In this pre-registered study, we manipulated threat imminence to activate the entire defensive brain circuitry, and assess the impact of different defensive responses on risky helping behaviour. Forty-nine participants underwent fMRI scanning while making trial-by-trial decisions about whether or not to help a co-participant avoid aversive shocks at the risk of receiving a shock themselves. Helping decisions were prompted under imminent and distal threat, based on the spatiotemporal distance to the administration of the shock to the co-participant. We found that greater engagement of reactive fear circuits (insula, ACC, PAG) during the threat presentation led to helping decisions, whereas engagement of cognitive fear circuits (hippocampus and vmPFC) preceded decisions not to help. Relying on representational similarity analysis, we identified how the defensive circuitry uniquely represented the threat to oneself, and the distress of the co-participant during the task. Importantly, we found that the strength with which the amygdala represented the threat to oneself, and not the other s distress, predicted decisions to help. Our results demonstrate that defensive neural circuits coordinating fast escape from immediate danger may also facilitate decisions to help others, potentially by engaging neurocognitive systems implicated in caregiving across mammals. Taken together, our findings provide novel insights into the proximal basis of altruistic responding, suggesting that defensive responses may play a more important role in helping than previously understood.

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Spatial Integration of Vascular Changes with Neural Activity in Mouse Cortex

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200203000-00013 ◽

2002 ◽

Vol 22 (3) ◽

pp. 353-360 ◽

Cited By ~ 49

Author(s):

Joseph P. Erinjeri ◽

Thomas A. Woolsey

Keyword(s):

Real Time ◽

Barrel Cortex ◽

Brain Regions ◽

Histochemical Staining ◽

Spatial Integration ◽

Intrinsic Signals ◽

Intrinsic Signal ◽

Cortical Columns ◽

Optical Intrinsic Signal ◽

Mouse Cortex

The authors evaluated representations of discretely activated, neighboring brain regions using real-time optical intrinsic signals by transcranial imaging with 540-nm and 610-nm broadband illumination of the mouse barrel cortex. Iron filings were glued to two neighboring whiskers (C2 + D2) that were stimulated magnetically, singly and together. Real-time images were collected, averaged, and analyzed statistically. Postmortem filling of arteries with fluorescent beads was shown in relation to histochemical staining of barrels to accurately relate surface changes to functional cortical columns. Significant optical intrinsic signal changes are related to overlapping distributions of arterioles that feed the two separate areas. Activation of adjacent and interacting cortical columns leads not only to increased magnitude of vascular responses in those columns, but also to wider spatial extent of absorption changes occurring principally in areas of cortex fed by vessels upstream of the active cortex. The localization of changing hemoglobin absorption around upstream blood vessels and their vascular domains suggests that propagated vasodilation of upstream parent vessels is greater when vasodilatory signals from separate areas of active cortex converge on common arterioles that feed them.

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Inhibitory Interneurons and their Circuit Motifs in the Many Layers of the Barrel Cortex

Neuroscience ◽

10.1016/j.neuroscience.2017.05.027 ◽

2018 ◽

Vol 368 ◽

pp. 132-151 ◽

Cited By ~ 55

Author(s):

Dirk Feldmeyer ◽

Guanxiao Qi ◽

Vishalini Emmenegger ◽

Jochen F. Staiger

Keyword(s):

Barrel Cortex ◽

Inhibitory Interneurons ◽

The Many

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Coupling of tactile LFP signals between mouse cortex and olfactory bulb

10.1101/144279 ◽

2017 ◽

Author(s):

Ana Parabucki ◽

Ilan Lampl

Keyword(s):

Olfactory Bulb ◽

Local Field ◽

Orbitofrontal Cortex ◽

Barrel Cortex ◽

Brain Activity ◽

Field Potential ◽

Field Potentials ◽

Mouse Cortex ◽

Highly Correlated ◽

Potential Signal

SummaryLocal field potentials are an important measure of brain activity and have been used to address various mechanistic and behavioral questions. We revealed a prominent whisker evoked local field potential signal in the olfactory bulb and investigated its physiology. This signal, dependent on barrel cortex activation and highly correlated with its local activity, represented a pure volume conductance signal that was sourced back to the activity in the ventro-lateral orbitofrontal cortex, located a few millimeters away. Thus, we suggest that special care should be taken when acquiring and interpreting LFP data.

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Hand before foot? Cortical somatotopy suggests manual dexterity is primitive and evolved independently of bipedalism

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2012.0417 ◽

2013 ◽

Vol 368 (1630) ◽

pp. 20120417 ◽

Cited By ~ 18

Author(s):

Teruo Hashimoto ◽

Kenichi Ueno ◽

Akitoshi Ogawa ◽

Takeshi Asamizuya ◽

Chisato Suzuki ◽

...

Keyword(s):

Tool Use ◽

Sensorimotor Cortex ◽

Manual Dexterity ◽

The Other ◽

Bipedal Locomotion ◽

Neural Representations ◽

Brain Circuits ◽

Primary Sensorimotor Cortex ◽

Neural Mapping ◽

The Brain

People have long speculated whether the evolution of bipedalism in early hominins triggered tool use (by freeing their hands) or whether the necessity of making and using tools encouraged the shift to upright gait. Either way, it is commonly thought that one led to the other. In this study, we sought to shed new light on the origins of manual dexterity and bipedalism by mapping the neural representations in the brain of the fingers and toes of living people and monkeys. Contrary to the ‘hand-in-glove’ notion outlined above, our results suggest that adaptations underlying tool use evolved independently of those required for human bipedality. In both humans and monkeys, we found that each finger was represented separately in the primary sensorimotor cortex just as they are physically separated in the hand. This reflects the ability to use each digit independently, as required for the complex manipulation involved in tool use. The neural mapping of the subjects’ toes differed, however. In the monkeys, the somatotopic representation of the toes was fused, showing that the digits function predominantly as a unit in general grasping. Humans, by contrast, had an independent neurological representation of the big toe (hallux), suggesting association with bipedal locomotion. These observations suggest that the brain circuits for the hand had advanced beyond simple grasping, whereas our primate ancestors were still general arboreal quadrupeds. This early adaptation laid the foundation for the evolution of manual dexterity, which was preserved and enhanced in hominins. In hominins, a separate adaptation, involving the neural separation of the big toe, apparently occurred with bipedality. This accords with the known fossil evidence, including the recently reported hominin fossils which have been dated to 4.4 million years ago.

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Cerebellar Golgi cell models predict dendritic processing and mechanisms of synaptic plasticity

10.1101/2020.05.13.093906 ◽

2020 ◽

Author(s):

Stefano Masoli ◽

Alessandra Ottaviani ◽

Egidio D’Angelo

Keyword(s):

Initial Segment ◽

Granular Layer ◽

Spike Timing ◽

Inhibitory Interneurons ◽

Golgi Cells ◽

Basal Dendrites ◽

Dendritic Processing ◽

Axonal Initial Segment ◽

Voltage Dependent ◽

Apical Dendrites

AbstractThe Golgi cells are the main inhibitory interneurons of the cerebellar granular layer. Although recent works have highlighted the complexity of their dendritic organization and synaptic inputs, the mechanisms through which these neurons integrate complex input patterns remained unknown. Here we have used 8 detailed morphological reconstructions to develop multicompartmental models of Golgi cells, in which Na, Ca, and K channels were distributed along dendrites, soma, axonal initial segment and axon. The models faithfully reproduced a rich pattern of electrophysiological and pharmacological properties and predicted the operating mechanisms of these neurons. Basal dendrites turned out to be more tightly electrically coupled to the axon initial segment than apical dendrites. During synaptic transmission, parallel fibers caused slow Ca-dependent depolarizations in apical dendrites that boosted the axon initial segment encoder and Na-spike backpropagation into basal dendrites, while inhibitory synapses effectively shunted backpropagating currents. This oriented dendritic processing set up a coincidence detector controlling voltage-dependent NMDA receptor unblock in basal dendrites, which, by regulating local calcium influx, may provide the basis for spike-timing dependent plasticity anticipated by theory.Author SummaryThe Golgi cells are the main inhibitory interneurons of the cerebellum granular layer and play a fundamental role in controlling cerebellar processing. However, it was unclear how spikes are processed in the dendrites by specific sets of ionic channels and how they might contribute to integrate synaptic inputs and plasticity. Here we have developed detailed multicompartmental models of Golgi cells that faithfully reproduced a large set of experimental findings and revealed the nature of signal interchange between dendrites and axo-somatic compartments. A main prediction of the models is that synaptic activation of apical dendrites can effectively trigger spike generation in the axonal initial segment followed by rapid spike backpropagation into basal dendrites. Here, incoming mossy fiber inputs and backpropagating spikes regulate the voltage-dependent unblock of NMDA channels and the induction of spike timing-dependent plasticity (STDP). STDP, which was predicted by theory, may therefore be controlled by contextual information provided by parallel fibers and integrated in apical dendrites, supporting the view that spike timing is fundamental to control synaptic plasticity at the cerebellar input stage.

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Synchronized gamma-frequency inhibition in neocortex depends on excitatory-inhibitory interactions but not electrical synapses

Journal of Neurophysiology ◽

10.1152/jn.00071.2016 ◽

2016 ◽

Vol 116 (2) ◽

pp. 351-368 ◽

Cited By ~ 9

Author(s):

Garrett T. Neske ◽

Barry W. Connors

Keyword(s):

Pyramidal Neurons ◽

Barrel Cortex ◽

Pyramidal Cells ◽

Inhibitory Interneurons ◽

Electrical Synapses ◽

Postsynaptic Currents ◽

Gamma Frequency ◽

Up States ◽

Inhibitory Interactions

Synaptic inhibition plays a crucial role in the precise timing of spiking activity in the cerebral cortex. Synchronized, rhythmic inhibitory activity in the gamma (30–80 Hz) range is thought to be especially important for the active, information-processing neocortex, but the circuit mechanisms that give rise to synchronized inhibition are uncertain. In particular, the relative contributions of reciprocal inhibitory connections, excitatory-inhibitory interactions, and electrical synapses to precise spike synchrony among inhibitory interneurons are not well understood. Here we describe experiments on mouse barrel cortex in vitro as it spontaneously generates slow (<1 Hz) oscillations (Up and Down states). During Up states, inhibitory postsynaptic currents (IPSCs) are generated at gamma frequencies and are more synchronized than excitatory postsynaptic currents (EPSCs) among neighboring pyramidal cells. Furthermore, spikes in homotypic pairs of interneurons are more synchronized than in pairs of pyramidal cells. Comparing connexin36 knockout and wild-type animals, we found that electrical synapses make a minimal contribution to synchronized inhibition during Up states. Estimations of the delays between EPSCs and IPSCs in single pyramidal cells showed that excitation often preceded inhibition by a few milliseconds. Finally, tonic optogenetic activation of different interneuron subtypes in the absence of excitation led to only weak synchrony of IPSCs in pairs of pyramidal neurons. Our results suggest that phasic excitatory inputs are indispensable for synchronized spiking in inhibitory interneurons during Up states and that electrical synapses play a minimal role.

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