Project description:Olfactory cortex pyramidal cells integrate sensory input from olfactory bulb mitral and tufted (M/T) cells and project axons back to the bulb. However, the impact of cortical feedback projections on olfactory bulb circuits is unclear. Here, we selectively express channelrhodopsin-2 in olfactory cortex pyramidal cells and show that cortical feedback projections excite diverse populations of bulb interneurons. Activation of cortical fibers directly excites GABAergic granule cells, which in turn inhibit M/T cells. However, we show that cortical inputs preferentially target short axon cells that drive feedforward inhibition of granule cells. In vivo, activation of olfactory cortex that only weakly affects spontaneous M/T cell firing strongly gates odor-evoked M/T cell responses: cortical activity suppresses odor-evoked excitation and enhances odor-evoked inhibition. Together, these results indicate that although cortical projections have diverse actions on olfactory bulb microcircuits, the net effect of cortical feedback on M/T cells is an amplification of odor-evoked inhibition.
Project description:After entering the cerebral cortex, sensory information spreads through six different horizontal neuronal layers that are interconnected by vertical axonal projections. It is believed that through these projections layers can influence each other's response to sensory stimuli, but the specific role that each layer has in cortical processing is still poorly understood. Here we show that layer six in the primary visual cortex of the mouse has a crucial role in controlling the gain of visually evoked activity in neurons of the upper layers without changing their tuning to orientation. This gain modulation results from the coordinated action of layer six intracortical projections to superficial layers and deep projections to the thalamus, with a substantial role of the intracortical circuit. This study establishes layer six as a major mediator of cortical gain modulation and suggests that it could be a node through which convergent inputs from several brain areas can regulate the earliest steps of cortical visual processing.
Project description:Neuronal microcircuits in the superficial layers of the mammalian cortex provide the substrate for associative cortical computation. Inhibitory interneurons constitute an essential component of the circuitry and are fundamental to the integration of local and long-range information. Here we report that, during early development, superficially positioned Reelin-expressing neurogliaform interneurons in the mouse somatosensory cortex receive afferent innervation from both cortical and thalamic excitatory sources. Attenuation of ascending sensory, but not intracortical, excitation leads to axo-dendritic morphological defects in these interneurons. Moreover, abrogation of the NMDA receptors through which the thalamic inputs signal results in a similar phenotype, as well as in the selective loss of thalamic and a concomitant increase in intracortical connectivity. These results suggest that thalamic inputs are critical in determining the balance between local and long-range connectivity and are fundamental to the proper integration of Reelin-expressing interneurons into nascent cortical circuits.
Project description:BACKGROUND:To dissect the intricate workings of neural circuits, it is essential to gain precise control over subsets of neurons while retaining the ability to monitor larger-scale circuit dynamics. This requires the ability to both evoke and record neural activity simultaneously with high spatial and temporal resolution. NEW METHOD:In this paper we present approaches that address this need by combining micro-electrocorticography (?ECoG) with optogenetics in ways that avoid photovoltaic artifacts. RESULTS:We demonstrate that variations of this approach are broadly applicable across three commonly studied mammalian species - mouse, rat, and macaque monkey - and that the recorded ?ECoG signal shows complex spectral and spatio-temporal patterns in response to optical stimulation. COMPARISON WITH EXISTING METHODS:While optogenetics provides the ability to excite or inhibit neural subpopulations in a targeted fashion, large-scale recording of resulting neural activity remains challenging. Recent advances in optical physiology, such as genetically encoded Ca(2+) indicators, are promising but currently do not allow simultaneous recordings from extended cortical areas due to limitations in optical imaging hardware. CONCLUSIONS:We demonstrate techniques for the large-scale simultaneous interrogation of cortical circuits in three commonly used mammalian species.
Project description:Many circuits in the mammalian brain are organized in a topographic or columnar manner. These circuits could be activated-in ways that reveal circuit function or restore function after disease-by an artificial stimulation system that is capable of independently driving local groups of neurons. Here we present a simple custom microscope called ProjectorScope 1 that incorporates off-the-shelf parts and a liquid crystal display (LCD) projector to stimulate surface brain regions that express channelrhodopsin-2 (ChR2). In principle, local optogenetic stimulation of the brain surface with optical projection systems might not produce local activation of a highly interconnected network like the cortex, because of potential stimulation of axons of passage or extended dendritic trees. However, here we demonstrate that the combination of virally mediated ChR2 expression levels and the light intensity of ProjectorScope 1 is capable of producing local spatial activation with a resolution of ∼200-300 μm. We use the system to examine the role of cortical activity in the experience-dependent emergence of motion selectivity in immature ferret visual cortex. We find that optogenetic cortical activation alone-without visual stimulation-is sufficient to produce increases in motion selectivity, suggesting the presence of a sharpening mechanism that does not require precise spatiotemporal activation of the visual system. These results demonstrate that optogenetic stimulation can sculpt the developing brain.
Project description:Animals perform innate behaviors that are stereotyped responses to specific evolutionarily relevant stimuli in the absence of prior learning or experience. These behaviors can be reduced to an axis of valence, whereby specific odors evoke approach and avoidance. The cortical amygdala (plCoA) mediates innate attraction and aversion to odor. However, little is known about how this brain area gives rise to behaviors of opposing motivational valence. Here, we sought to define the circuit features of plCoA that give rise to innate olfactory behaviors of valence. We characterized the physiology, gene expression, and projections of this structure, identifying a divergent, topographic organization that selectively controls innate attraction and avoidance to odor. First, we examined odor-evoked responses in these areas and found sparse encoding of odor identity, but not valence. We next considered a topographic organization and found that optogenetic stimulation of the anterior and posterior domains of plCoA elicits attraction and avoidance, respectively, suggesting a functional axis for valence. Using single cell and spatial RNA sequencing, we identified the molecular cell types in plCoA, revealing an anteroposterior gradient in cell types, whereby anterior glutamatergic neurons preferentially express Slc17a6 and posterior neurons express Slc17a7. Activation of these respective cell types recapitulates appetitive and aversive valence behaviors, and chemogenetic inhibition reveals partial necessity for valence responses to innate appetitive or aversive odors. Finally, we identified topographically organized circuits defined by projections, whereby anterior neurons preferentially project to medial amygdala, and posterior neurons preferentially project to nucleus accumbens, which are respectively sufficient and necessary for innate negative and positive olfactory valence. Together, these data advance our understanding of how the olfactory system generates stereotypic, hardwired attraction and avoidance, and supports a model whereby distinct, topographically distributed plCoA populations direct innate olfactory valence responses by signaling to divergent valence-specific targets, linking upstream olfactory identity to downstream valence behaviors, through a population code. This represents a novel circuit motif in which valence encoding is represented not by the firing properties of individual neurons, but by population level identity encoding that is routed through divergent targets to mediate distinct valence.
Project description:Despite the fact that strong trial-to-trial correlated variability in responses has been reported in many cortical areas, recent evidence suggests that neuronal correlations are much lower than previously thought. Here, we used multicontact laminar probes to revisit the issue of correlated variability in primary visual (V1) cortical circuits. We found that correlations between neurons depend strongly on local network context--whereas neurons in the input (granular) layers showed virtually no correlated variability, neurons in the output layers (supragranular and infragranular) exhibited strong correlations. The laminar dependence of noise correlations is consistent with recurrent models in which neurons in the granular layer receive intracortical inputs from nearby cells, whereas supragranular and infragranular layer neurons receive inputs over larger distances. Contrary to expectation that the output cortical layers encode stimulus information most accurately, we found that the input network offers superior discrimination performance compared to the output networks.
Project description:Correlated spiking is often observed in cortical circuits, but its functional role is controversial. It is believed that correlations are a consequence of shared inputs between nearby neurons and could severely constrain information decoding. Here we show theoretically that recurrent neural networks can generate an asynchronous state characterized by arbitrarily low mean spiking correlations despite substantial amounts of shared input. In this state, spontaneous fluctuations in the activity of excitatory and inhibitory populations accurately track each other, generating negative correlations in synaptic currents which cancel the effect of shared input. Near-zero mean correlations were seen experimentally in recordings from rodent neocortex in vivo. Our results suggest a reexamination of the sources underlying observed correlations and their functional consequences for information processing.
Project description:The traditional view of neural computation in the cerebral cortex holds that sensory neurons are specialized, i.e., selective for certain dimensions of sensory stimuli. This view was challenged by evidence of contextual interactions between stimulus dimensions in which a neuron's response to one dimension strongly depends on other dimensions. Here, we use methods of mathematical modeling, psychophysics, and electrophysiology to address shortcomings of the traditional view. Using a model of a generic cortical circuit, we begin with the simple demonstration that cortical responses are always distributed among neurons, forming characteristic waveforms, which we call neural waves. When stimulated by patterned stimuli, circuit responses arise by interference of neural waves. Results of this process depend on interaction between stimulus dimensions. Comparison of modeled responses with responses of biological vision makes it clear that the framework of neural wave interference provides a useful alternative to the standard concept of neural computation.
Project description:Inhibitory neurons play a fundamental role in cortical computation and behavior. Recent technological advances, such as two photon imaging, targeted in vivo recording, and molecular profiling, have improved our understanding of the function and diversity of cortical interneurons, but for technical reasons most work has been directed towards inhibitory neurons in the superficial cortical layers. Here we review current knowledge specifically on layer 5 (L5) inhibitory microcircuits, which play a critical role in controlling cortical output. We focus on recent work from the well-studied rodent barrel cortex, but also draw on evidence from studies in primary visual cortex and other cortical areas. The diversity of both deep inhibitory neurons and their pyramidal cell targets make this a challenging but essential area of study in cortical computation and sensory processing.