Rapid odor processing by layer 2 subcircuits in lateral entorhinal cortex.

Olfactory information is encoded in lateral entorhinal cortex (LEC) by two classes of layer 2 (L2) principal neurons: fan and pyramidal cells. However, the functional properties of L2 cells and how they contribute to odor coding are unclear. Here, we show in awake mice that L2 cells respond to odors early during single sniffs and that LEC is essential for rapid discrimination of both odor identity and intensity.

Interhemispheric Callosal Projections Sharpen Frequency Tuning and Enforce Response Fidelity in Primary Auditory Cortex.

Sensory cortical areas receive glutamatergic callosal projections that link information processing between brain hemispheres. In primary auditory cortex (A1), ipsilateral principal cells from a particular tonotopic region project to neurons in matching frequency space of the contralateral cortex. However, the role of interhemispheric projections in shaping cortical responses to sound and frequency tuning in awake animals is unclear.

Arousal regulates frequency tuning in primary auditory cortex.

Changes in arousal influence cortical sensory representations, but the synaptic mechanisms underlying arousal-dependent modulation of cortical processing are unclear. Here, we use 2-photon Ca imaging in the auditory cortex of awake mice to show that heightened arousal, as indexed by pupil diameter, broadens frequency-tuned activity of layer 2/3 (L2/3) pyramidal cells. Sensory representations are less sparse, and the tuning of nearby cells more similar when arousal increases.

Fear Learning Regulates Cortical Sensory Representations by Suppressing Habituation.

Projections from auditory cortex to the amygdala are thought to contribute to the induction of auditory fear learning. In addition, fear conditioning has been found to enhance cortical responses to conditioned tones, suggesting that cortical plasticity contributes to fear learning. However, the functional role of auditory cortex in the retrieval of fear memories is unclear and how fear learning regulates cortical sensory representations is not well understood.

Network-Level Control of Frequency Tuning in Auditory Cortex.

Lateral inhibition is a fundamental circuit operation that sharpens the tuning properties of cortical neurons. This operation is classically attributed to an increase in GABAergic synaptic input triggered by non-preferred stimuli. Here we use in vivo whole-cell recording and two-photon Ca imaging in awake mice to show that lateral inhibition shapes frequency tuning in primary auditory cortex via an unconventional mechanism: non-preferred tones suppress both excitatory and inhibitory synaptic inputs onto layer 2/3 cells ("network suppression").

Flexible Sensory Representations in Auditory Cortex Driven by Behavioral Relevance.

Animals require the ability to ignore sensory stimuli that have no consequence yet respond to the same stimuli when they become useful. However, the brain circuits that govern this flexibility in sensory processing are not well understood. Here we show in mouse primary auditory cortex (A1) that daily passive sound exposure causes a long-lasting reduction in representations of the experienced sound by layer 2/3 pyramidal cells.

Somatostatin cells regulate sensory response fidelity via subtractive inhibition in olfactory cortex.

Diverse types of local GABAergic interneurons shape the cortical representation of sensory information. Here we show how somatostatin-expressing interneurons (SOM cells) contribute to odor coding in mouse olfactory cortex. We find that odor-tuned SOM cells regulate principal cells through a purely subtractive operation that is independent of odor identity or intensity.

Broadcasting of cortical activity to the olfactory bulb.

Odor representations are initially formed in the olfactory bulb, which contains a topographic glomerular map of odor molecular features. The bulb transmits sensory information directly to piriform cortex, where it is encoded by distributed ensembles of pyramidal cells without spatial order. Intriguingly, piriform cortex pyramidal cells project back to the bulb, but the information contained in this feedback projection is unknown.

Single dendrite-targeting interneurons generate branch-specific inhibition.

Microcircuits composed of dendrite-targeting inhibitory interneurons and pyramidal cells (PCs) are fundamental elements of cortical networks, however, the impact of individual interneurons on pyramidal dendrites is unclear. Here, we combine paired recordings and calcium imaging to determine the spatial domain over which single dendrite-targeting interneurons influence PCs in olfactory cortex. We show that a major action of individual interneurons is to inhibit dendrites in a branch-specific fashion.

Parvalbumin-expressing interneurons linearly control olfactory bulb output.

In the olfactory bulb, odor representations by principal mitral cells are modulated by local inhibitory circuits. While dendrodendritic synapses between mitral and granule cells are typically thought to be a major source of this modulation, the contributions of other inhibitory neurons remain unclear. Here we demonstrate the functional properties of olfactory bulb parvalbumin-expressing interneurons (PV cells) and identify their important role in odor coding.

Cortical feedback control of olfactory bulb circuits.

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.

Dynamic sensory representations in the olfactory bulb: modulation by wakefulness and experience.

How are sensory representations in the brain influenced by the state of an animal? Here we use chronic two-photon calcium imaging to explore how wakefulness and experience shape odor representations in the mouse olfactory bulb. Comparing the awake and anesthetized state, we show that wakefulness greatly enhances the activity of inhibitory granule cells and makes principal mitral cell odor responses more sparse and temporally dynamic. In awake mice, brief repeated odor experience leads to a gradual and long-lasting (months) weakening of mitral cell odor representations.

How inhibition shapes cortical activity.

Cortical processing reflects the interplay of synaptic excitation and synaptic inhibition. Rapidly accumulating evidence is highlighting the crucial role of inhibition in shaping spontaneous and sensory-evoked cortical activity and thus underscores how a better knowledge of inhibitory circuits is necessary for our understanding of cortical function. We discuss current views of how inhibition regulates the function of cortical neurons and point to a number of important open questions.

A major role for intracortical circuits in the strength and tuning of odor-evoked excitation in olfactory cortex.

In primary sensory cortices, there are two main sources of excitation: afferent sensory input relayed from the periphery and recurrent intracortical input. Untangling the functional roles of these two excitatory pathways is fundamental for understanding how cortical neurons process sensory stimuli. Odor representations in the primary olfactory (piriform) cortex depend on excitatory sensory afferents from the olfactory bulb.

Linking neuronal ensembles by associative synaptic plasticity.

Synchronized activity in ensembles of neurons recruited by excitatory afferents is thought to contribute to the coding information in the brain. However, the mechanisms by which neuronal ensembles are generated and modified are not known. Here we show that in rat hippocampal slices associative synaptic plasticity enables ensembles of neurons to change by incorporating neurons belonging to different ensembles.

Pyramidal cells in piriform cortex receive convergent input from distinct olfactory bulb glomeruli.

Pyramidal cells in piriform cortex integrate sensory information from multiple olfactory bulb mitral and tufted (M/T) cells. However, whether M/T cells belonging to different olfactory bulb glomeruli converge onto individual cortical cells is unclear. Here we use calcium imaging in an olfactory bulb-cortex slice preparation to provide direct evidence that neurons in piriform cortex receive convergent synaptic input from different glomeruli.

From dendrite to soma: dynamic routing of inhibition by complementary interneuron microcircuits in olfactory cortex.

Diverse inhibitory pathways shape cortical information processing; however, the relevant interneurons recruited by sensory stimuli and how they impact principal cells are unclear. Here we show that two major interneuron circuits govern dynamic inhibition in space and time within the olfactory cortex. Dendritic-targeting layer 1 interneurons receive strong input from the olfactory bulb and govern early-onset feedforward inhibition.

Odor representations in mammalian cortical circuits.

Spatial and temporal activity patterns of olfactory bulb projection neurons underlie the initial representations of odors in the brain. However, olfactory perception ultimately requires the integration of olfactory bulb output in higher cortical brain regions. Recent studies reveal that odor representations are sparse and highly distributed in the rodent primary olfactory (piriform) cortex.

Calcium-permeable AMPA receptors mediate glutamatergic signaling in neural precursor cells of the postnatal olfactory bulb.

Neural precursor cells (NPCs) in the mammalian olfactory bulb give rise to local inhibitory neurons that integrate into existing circuitry throughout adult life. However, the functional properties of neurotransmitter receptors expressed by NPCs are not well understood. In this study, we use patch-clamp recording and calcium imaging to explore the properties of glutamate receptors expressed by NPCs in the olfactory bulb subependymal layer.

Postsynaptic mechanisms govern the differential excitation of cortical neurons by thalamic inputs.

Thalamocortical (TC) afferents relay sensory input to the cortex by making synapses onto both excitatory regular-spiking principal cells (RS cells) and inhibitory fast-spiking interneurons (FS cells). This divergence plays a crucial role in coordinating excitation with inhibition during the earliest steps of somatosensory processing in the cortex. Although the same TC afferents contact both FS and RS cells, FS cells receive larger and faster excitatory inputs from individual TC afferents.

Odor representations in olfactory cortex: "sparse" coding, global inhibition, and oscillations.

The properties of cortical circuits underlying central representations of sensory stimuli are poorly understood. Here we use in vivo cell-attached and whole-cell voltage-clamp recordings to reveal how excitatory and inhibitory synaptic input govern odor representations in rat primary olfactory (piriform) cortex. We show that odors evoke spiking activity that is sparse across the cortical population.

L-type calcium channels govern calcium signaling in migrating newborn neurons in the postnatal olfactory bulb.

Newborn inhibitory neurons migrate into existing neural circuitry in the olfactory bulb throughout the lifetime of adult mammals. While many factors contribute to the maturation of neural circuits, intracellular calcium is believed to play an important role in regulating cell migration and the development of neural systems. However, the factors underlying calcium signaling within newborn neurons in the postnatal olfactory bulb are not well understood.

An early critical period for long-term plasticity and structural modification of sensory synapses in olfactory cortex.

Critical periods for plasticity of thalamic sensory inputs play an important role in developing neocortical circuits. During an early postnatal time window, pyramidal cells of visual, auditory, and somatosensory cortex undergo structural refinement and possess an enhanced ability for activity-dependent synaptic plasticity. In olfactory cortex, however, pyramidal cells receive direct sensory input from the olfactory bulb, and it is unclear whether the development of olfactory sensory circuits is governed by a critical period.

Strong single-fiber sensory inputs to olfactory cortex: implications for olfactory coding.

Olfactory information is first encoded in a combinatorial fashion by olfactory bulb glomeruli, which individually represent distinct chemical features of odors. This information is then transmitted to piriform (olfactory) cortex, via axons of olfactory bulb mitral and tufted (M/T) cells, where it is presumed to form the odor percept. However, mechanisms governing the integration of sensory information in mammalian olfactory cortex are unclear.

Synapse-specific downregulation of NMDA receptors by early experience: a critical period for plasticity of sensory input to olfactory cortex.

Olfaction is required at birth for survival; however, little is known about the maturation of olfactory cortical circuits. Here we show that in vivo sensory experience mediates the development of excitatory transmission in pyramidal neurons of rat olfactory cortex. We find a postnatal critical period during which there is an experience-dependent increase in the contribution of AMPARs versus NMDARs to transmission at primary sensory synapses but not associational inputs.