One of the striking manifestations of neuronal population activity is that of rhythmic oscillations in the local field potential. It is thought that such oscillatory patterns, including phase-amplitude coupling (PAC) and inter-regional synchrony, may represent forms of local and long-range cortical computations, respectively. Although it has been speculated that these two oscillatory patterns are functionally related, and bind disparate cortical assemblies to one another at different timescales, there is little direct evidence to support this hypothesis. We have demonstrated recently that theta to high-gamma PAC and interlaminar phase coherence at theta frequencies can be generated in human cortical slices maintained in vitro. Here we show that not only do such oscillatory patterns exist within human temporal neocortex, but that the strength of one is related to the strength of the other. We demonstrate that at theta frequencies, metrics of temporal synchrony between superficial and deep cortical laminae (phase-dependent power correlations, and phase coherence) are correlated to the magnitude of intralaminar PAC between theta and high-gamma. Specifically, our results suggest that interlaminar communication within human temporal neocortex and local laminar excitability are linked to one another through a dependence mediated by theta oscillations. More generally, our results provide evidence for the hypothesis that theta oscillations may coordinate inter-areal excitability in the human brain.
Wednesday, 26 November 2014
Mesoscale Transcranial Spontaneous Activity Mapping in GCaMP3 Transgenic Mice Reveals Extensive Reciprocal Connections between Areas of Somatomotor Cortex
Transgenic mice expressing genetically encoded activity indicators are an attractive means of mapping mesoscopic regional functional cortical connectivity given widespread stable and cell-specific expression compatible with chronic recordings. Cortical functional connectivity was evaluated using wide-field imaging in lightly anesthetized Emx1-creXRosa26-GCaMP3 mice expressing calcium sensor in cortical neurons. Challenges exist because green fluorescence signals overlap with endogenous activity-dependent autofluorescence and are affected by changes in blood volume and oxygenation. Under the conditions used for imaging and analysis (0.1–1 Hz frequency band), autofluorescence and hemodynamic effects contributed 3% and 8% of the SD of spontaneous activity-dependent GCaMP3 fluorescence when signals were recorded through intact bone. To evaluate the accuracy and sensitivity of this approach, the topology of functional connections between somatomotor cortex (primary S1 and secondary S2 somatosensory, and primary motor cortex M1) was estimated. During sequences of spontaneous activity, calcium signals recorded at each location of area S1 were correlated with activity in contralateral area S1, ipsilateral area S2, and bilateral areas M1. Reciprocal results were observed when "seed pixels" were placed in S2 and M1. Coactivation of areas implies functional connections but could also be attributed to both regions receiving common upstream drive. These apparent connections revealed during spontaneous activity coactivation by GCaMP3 were confirmed by intracortical microstimulation but were more difficult to detect using intrinsic signals from reflected red light. We anticipate GCAMP wide-field imaging will enable longitudinal studies during plasticity paradigms or after models of CNS disease, such as stroke, where the weighting within these connectivity maps may be altered.
Dynamic Divisive Normalization Predicts Time-Varying Value Coding in Decision-Related Circuits
Normalization is a widespread neural computation, mediating divisive gain control in sensory processing and implementing a context-dependent value code in decision-related frontal and parietal cortices. Although decision-making is a dynamic process with complex temporal characteristics, most models of normalization are time-independent and little is known about the dynamic interaction of normalization and choice. Here, we show that a simple differential equation model of normalization explains the characteristic phasic-sustained pattern of cortical decision activity and predicts specific normalization dynamics: value coding during initial transients, time-varying value modulation, and delayed onset of contextual information. Empirically, we observe these predicted dynamics in saccade-related neurons in monkey lateral intraparietal cortex. Furthermore, such models naturally incorporate a time-weighted average of past activity, implementing an intrinsic reference-dependence in value coding. These results suggest that a single network mechanism can explain both transient and sustained decision activity, emphasizing the importance of a dynamic view of normalization in neural coding.
Precise Detection of Direct Glomerular Input Duration by the Olfactory Bulb
Sensory neuron input to the olfactory bulb (OB) was activated precisely for different durations with blue light in mice expressing channelrhodopsin-2 in olfactory sensory neurons. Behaviorally the mice discriminated differences of 10 ms in duration of direct glomerular activation. In addition, a subset of mitral/tufted cells in the OB of awake mice responded tonically therefore conveying information on stimulus duration. Our study provides evidence that duration of the input to glomeruli not synchronized to sniffing is detected. This potent cue may be used to obtain information on puffs in odor plumes.
A Role for Mixed Corollary Discharge and Proprioceptive Signals in Predicting the Sensory Consequences of Movements
Animals must distinguish behaviorally relevant patterns of sensory stimulation from those that are attributable to their own movements. In principle, this distinction could be made based on internal signals related to motor commands, known as corollary discharge (CD), sensory feedback, or some combination of both. Here we use an advantageous model system—the electrosensory lobe (ELL) of weakly electric mormyrid fish—to directly examine how CD and proprioceptive feedback signals are transformed into negative images of the predictable electrosensory consequences of the fish's motor commands and/or movements. In vivo recordings from ELL neurons and theoretical modeling suggest that negative images are formed via anti-Hebbian plasticity acting on random, nonlinear mixtures of CD and proprioception. In support of this, we find that CD and proprioception are randomly mixed in spinal mossy fibers and that properties of granule cells are consistent with a nonlinear recoding of these signals. The mechanistic account provided here may be relevant to understanding how internal models of movement consequences are implemented in other systems in which similar components (e.g., mixed sensory and motor signals and synaptic plasticity) are found.
Immune-Induced Fever Is Mediated by IL-6 Receptors on Brain Endothelial Cells Coupled to STAT3-Dependent Induction of Brain Endothelial Prostaglandin Synthesis
The cytokine IL-6, which is released upon peripheral immune challenge, is critical for the febrile response, but the mechanism by which IL-6 is pyrogenic has remained obscure. Here we generated mice with deletion of the membrane bound IL-6 receptor α (IL-6Rα) on neural cells, on peripheral nerves, on fine sensory afferent fibers, and on brain endothelial cells, respectively, and examined its role for the febrile response to peripherally injected lipopolysaccharide. We show that IL-6Rα on neural cells, peripheral nerves, and fine sensory afferents are dispensable for the lipopolysaccharide-induced fever, whereas IL-6Rα in the brain endothelium plays an important role. Hence deletion of IL-6Rα on brain endothelial cells strongly attenuated the febrile response, and also led to reduced induction of the prostaglandin synthesizing enzyme Cox-2 in the hypothalamus, the temperature-regulating center in the brain, as well as reduced expression of SOCS3, suggesting involvement of the STAT signaling pathway. Furthermore, deletion of STAT3 in the brain endothelium also resulted in attenuated fever. These data show that IL-6, when endogenously released during systemic inflammation, is pyrogenic by binding to IL-6Rα on brain endothelial cells to induce prostaglandin synthesis in these cells, probably in concerted action with other peripherally released cytokines.
Temporal Integration of Cholinergic and GABAergic Inputs in Isolated Insect Mushroom Body Neurons Exposes Pairing-Specific Signal Processing
GABAergic modulation of neuronal activity plays a crucial role in physiological processes including learning and memory in both insects and mammals. During olfactory learning in honeybees (Apis mellifera) and Drosophila melanogaster the temporal relation between excitatory cholinergic and inhibitory GABAergic inputs critically affects learning. However, the cellular mechanisms of temporal integration of these antagonistic inputs are unknown. To address this question, we use calcium imaging of isolated honeybee and Drosophila Kenyon cells (KCs), which are targets of cholinergic and GABAergic inputs during olfactory learning. In the whole population of honeybee KCs we find that pairing of acetylcholine (ACh) and -aminobutyric acid (GABA) Comment: Please use the greek letter for gamma reduces the ACh-induced calcium influx, and depending on their temporal sequence, induces different forms of neuronal plasticity. After ACh–GABA pairing the calcium influx of a subsequent excitatory stimulus is increased, while GABA–ACh pairing affects the decay time leading to elevated calcium levels during the late phase of a subsequent excitatory stimulus. In an exactly defined subset of Drosophila KCs implicated in learning we find similar pairing-specific differences. Specifically the GABA–ACh pairing splits the KCs in two functional subgroups: one is only weakly inhibited by GABA and shows no neuronal plasticity and the other subgroup is strongly inhibited by GABA and shows elevated calcium levels during the late phase of a subsequent excitatory stimulus. Our findings provide evidence that insect KCs are capable of contributing to temporal processing of cholinergic and GABAergic inputs, which provides a neuronal mechanism of the differential temporal role of GABAergic inhibition during learning.
