Project description:Neurons in the cerebral cortex fire coincident action potentials during ongoing activity and in response to sensory inputs. These synchronized cell assemblies are fundamental to cortex function, yet basic dynamical aspects of their size and duration are largely unknown. Using 2-photon imaging of neurons in the superficial cortex of awake mice, we show that synchronized cell assemblies organize as scale-invariant avalanches that quadratically grow with duration. The quadratic avalanche scaling was only found for correlated neurons, required temporal coarse-graining to compensate for spatial subsampling of the imaged cortex, and suggested cortical dynamics to be critical as demonstrated in simulations of balanced E/I-networks. The corresponding time course of an inverted parabola with exponent of χ = 2 described cortical avalanches of coincident firing for up to 5 s duration over an area of 1 mm2. These parabolic avalanches maximized temporal complexity in the ongoing activity of prefrontal and somatosensory cortex and in visual responses of primary visual cortex. Our results identify a scale-invariant temporal order in the synchronization of highly diverse cortical cell assemblies in the form of parabolic avalanches.
Project description:High-level cortical systems for spatial navigation, including entorhinal grid cells, critically depend on input from the head direction system. We examined spiking rhythms and modes of synchrony between neurons participating in head direction networks for evidence of internal processing, independent of direct sensory drive, which may be important for grid cell function. We found that head direction networks of rats were segregated into at least two populations of neurons firing on alternate theta cycles (theta cycle skipping) with fixed synchronous or anti-synchronous relationships. Pairs of anti-synchronous theta cycle skipping neurons exhibited larger differences in head direction tuning, with a minimum difference of 40 degrees of head direction. Septal inactivation preserved the head direction signal, but eliminated theta cycle skipping of head direction cells and grid cell spatial periodicity. We propose that internal mechanisms underlying cycle skipping in head direction networks may be critical for downstream spatial computation by grid cells.
Project description:The architectonic type principle relates patterns of cortico-cortical connectivity to the relative architectonic differentiation of cortical regions. One mechanism through which the observed close relation between cortical architecture and connectivity may be established is the joint development of cortical areas and their connections in developmental time windows. Here, we describe a theoretical exploration of the possible mechanistic underpinnings of the architectonic type principle, by performing systematic computational simulations of cortical development. The main component of our in silico model was a developing two-dimensional cortical sheet, which was gradually populated by neurons that formed cortico-cortical connections. To assess different explanatory mechanisms, we varied the spatiotemporal trajectory of the simulated neurogenesis. By keeping the rules governing axon outgrowth and connection formation constant across all variants of simulated development, we were able to create model variants which differed exclusively by the specifics of when and where neurons were generated. Thus, all differences in the resulting connectivity were due to the variations in spatiotemporal growth trajectories. Our results demonstrated that a prescribed targeting of interareal connection sites was not necessary for obtaining a realistic replication of the experimentally observed relation between connection patterns and architectonic differentiation. Instead, we found that spatiotemporal interactions within the forming cortical sheet were sufficient if a small number of empirically well-grounded assumptions were met, namely planar, expansive growth of the cortical sheet around two points of origin as neurogenesis progressed, stronger architectonic differentiation of cortical areas for later neurogenetic time windows, and stochastic connection formation. Thus, our study highlights a potential mechanism of how relative architectonic differentiation and cortical connectivity become linked during development. We successfully predicted connectivity in two species, cat and macaque, from simulated cortico-cortical connection networks, which further underscored the general applicability of mechanisms through which the architectonic type principle can explain cortical connectivity in terms of the relative architectonic differentiation of cortical regions.
Project description:Sensory computations performed in the neocortex involve layer six (L6) cortico-cortical (CC) and cortico-thalamic (CT) signaling pathways. Developing an understanding of the physiological role of these circuits requires dissection of the functional specificity and connectivity of the underlying individual projection neurons. By combining whole-cell recording from identified L6 principal cells in the mouse primary visual cortex (V1) with modified rabies virus-based input mapping, we have determined the sensory response properties and upstream monosynaptic connectivity of cells mediating the CC or CT pathway. We show that CC-projecting cells encompass a broad spectrum of selectivity to stimulus orientation and are predominantly innervated by deep layer V1 neurons. In contrast, CT-projecting cells are ultrasparse firing, exquisitely tuned to orientation and direction information, and receive long-range input from higher cortical areas. This segregation in function and connectivity indicates that L6 microcircuits route specific contextual and stimulus-related information within and outside the cortical network.
Project description:The parabrachial nucleus (PB) in the upper brain stem tegmentum includes several neuronal subpopulations with a wide variety of connections and functions. A subpopulation of PB neurons projects axons directly to the cerebral cortex, and limbic areas of the cerebral cortex send a return projection directly to the PB. We used retrograde and Cre-dependent anterograde tracing to identify genetic markers and characterize this PB-cortical interconnectivity in mice. Cortical projections originate from glutamatergic PB neurons that contain Lmx1b (81%), estrogen receptor alpha (26%), and Satb2 (20%), plus mRNA for the neuropeptides cholecystokinin (Cck, 48%) and calcitonin gene-related peptide (Calca, 13%), with minimal contribution from FoxP2+ PB neurons (2%). Axons from the PB produce an extensive terminal field in an unmyelinated region of the insular cortex, extending caudally into the entorhinal cortex, and arcing rostrally through the dorsolateral prefrontal cortex, with a secondary terminal field in the medial prefrontal cortex. In return, layer 5 neurons in the insular cortex and other prefrontal areas, along with a dense cluster of cells dorsal to the claustrum, send a descending projection to subregions of the PB that contain cortically projecting neurons. This information forms the neuroanatomical basis for testing PB-cortical interconnectivity in arousal and interoception.
Project description:Suboptimal nitrogen availability is a primary constraint to plant growth. We used OpenSimRoot, a functional-structural plant/soil model, to test the hypothesis that larger root cortical cell size (CCS), reduced cortical cell file number (CCFN), and their interactions with root cortical aerenchyma (RCA) and lateral root branching density (LRBD) are useful adaptations to suboptimal soil nitrogen availability in maize (Zea mays). Reduced CCFN increased shoot dry weight over 80%. Reduced respiration, reduced nitrogen content, and reduced root diameter accounted for 23%, 20%, and 33% of increased shoot biomass, respectively. Large CCS increased shoot biomass by 24% compared with small CCS. When simulated independently, reduced respiration and reduced nutrient content increased the shoot biomass by 14% and 3%, respectively. However, increased root diameter resulting from large CCS decreased shoot biomass by 4% due to an increase in root metabolic cost. Under moderate N stress, integrated phenotypes with reduced CCFN, large CCS, and high RCA improved shoot biomass in silt loam and loamy sand soils. In contrast, integrated phenotypes composed of reduced CCFN, large CCS, and reduced LRBD had the greatest growth in silt loam, while phenotypes with reduced CCFN, large CCS, and high LRBD were the best performers in loamy sands. Our results support the hypothesis that larger CCS, reduced CCFN, and their interactions with RCA and LRBD could increase nitrogen acquisition by reducing root respiration and root nutrient demand. Phene synergisms may exist between CCS, CCFN, and LRBD. CCS and CCFN merit consideration for breeding cereal crops with improved nitrogen acquisition, which is critical for global food security.
Project description:To understand auditory cortical processing, the effective connectivity between 15 auditory cortical regions and 360 cortical regions was measured in 171 Human Connectome Project participants, and complemented with functional connectivity and diffusion tractography. 1. A hierarchy of auditory cortical processing was identified from Core regions (including A1) to Belt regions LBelt, MBelt, and 52; then to PBelt; and then to HCP A4. 2. A4 has connectivity to anterior temporal lobe TA2, and to HCP A5, which connects to dorsal-bank superior temporal sulcus (STS) regions STGa, STSda, and STSdp. These STS regions also receive visual inputs about moving faces and objects, which are combined with auditory information to help implement multimodal object identification, such as who is speaking, and what is being said. Consistent with this being a "what" ventral auditory stream, these STS regions then have effective connectivity to TPOJ1, STV, PSL, TGv, TGd, and PGi, which are language-related semantic regions connecting to Broca's area, especially BA45. 3. A4 and A5 also have effective connectivity to MT and MST, which connect to superior parietal regions forming a dorsal auditory "where" stream involved in actions in space. Connections of PBelt, A4, and A5 with BA44 may form a language-related dorsal stream.
Project description:Non-random connectivity can emerge without structured external input driven by activity-dependent mechanisms of synaptic plasticity based on precise spiking patterns. Here we analyze the emergence of global structures in recurrent networks based on a triplet model of spike timing dependent plasticity (STDP), which depends on the interactions of three precisely-timed spikes, and can describe plasticity experiments with varying spike frequency better than the classical pair-based STDP rule. We derive synaptic changes arising from correlations up to third-order and describe them as the sum of structural motifs, which determine how any spike in the network influences a given synaptic connection through possible connectivity paths. This motif expansion framework reveals novel structural motifs under the triplet STDP rule, which support the formation of bidirectional connections and ultimately the spontaneous emergence of global network structure in the form of self-connected groups of neurons, or assemblies. We propose that under triplet STDP assembly structure can emerge without the need for externally patterned inputs or assuming a symmetric pair-based STDP rule common in previous studies. The emergence of non-random network structure under triplet STDP occurs through internally-generated higher-order correlations, which are ubiquitous in natural stimuli and neuronal spiking activity, and important for coding. We further demonstrate how neuromodulatory mechanisms that modulate the shape of the triplet STDP rule or the synaptic transmission function differentially promote structural motifs underlying the emergence of assemblies, and quantify the differences using graph theoretic measures.
Project description:We previously reported that pan-cortical effects occur when cognitive tasks end afterdischarges. For this report, we analyzed wavelet cross-coherence changes during cognitive tasks used to terminate afterdischarges studying multiple time segments and multiple groups of inter-electrode-con distances. We studied 12 patients with intractable epilepsy, with 970 implanted electrode contacts, and 39,871 electrode contact combinations. When cognitive tasks ended afterdischarges, coherence varied similarly across the cortex throughout the tasks, but there were gradations with time, distance, and frequency: (1) They tended to progressively decrease relative to baseline with time and then to increase toward baseline when afterdischarges ended. (2) During most time segments, decreases from baseline were largest for the closest inter-contact distances, moderate for intermediate inter-contact distances, and smallest for the greatest inter-contact distances. With respect to our patients' intractable epilepsy, the changes found suggest that future therapies might treat regions beyond those closest to regions of seizure onset and treat later in a seizure's evolution. Similar considerations might apply to other disorders. Our findings also suggest that cognitive tasks can result in pan-cortical coherence changes that participate in underlying attention, perhaps complementing the better-known regional mechanisms.