Fast-spiking interneuron detonation drives high-fidelity inhibition in the olfactory bulb.

Inhibitory circuits in the mammalian olfactory bulb (OB) dynamically reformat olfactory information as it propagates from peripheral receptors to downstream cortex. To gain mechanistic insight into how specific OB interneuron types support this sensory processing, we examine unitary synaptic interactions between excitatory mitral and tufted cells (MTCs), the OB projection neurons, and a conserved population of anaxonic external plexiform layer interneurons (EPL-INs) using pair and quartet whole-cell recordings in acute mouse brain slices. Physiological, morphological, neurochemical, and synaptic analyses divide EPL-INs into distinct subtypes and reveal that parvalbumin-expressing fast-spiking EPL-INs (FSIs) perisomatically innervate MTCs with release-competent dendrites and synaptically detonate to mediate fast, short-latency recurrent and lateral inhibition. Sparse MTC synchronization supralinearly increases this high-fidelity inhibition, while sensory afferent activation combined with single-cell silencing reveals that individual FSIs account for a substantial fraction of total network-driven MTC lateral inhibition. OB output is thus powerfully shaped by detonation-driven high-fidelity perisomatic inhibition.

Fast-spiking interneuron detonation drives high-fidelity inhibition in the olfactory bulb.

Inhibitory circuits in the mammalian olfactory bulb (OB) dynamically reformat olfactory information as it propagates from peripheral receptors to downstream cortex. To gain mechanistic insight into how specific OB interneuron types support this sensory processing, we examine unitary synaptic interactions between excitatory mitral and tufted cells (MTCs), the OB projection cells, and a conserved population of anaxonic external plexiform layer interneurons (EPL-INs) using pair and quartet whole-cell recordings in acute mouse brain slices. Physiological, morphological, neurochemical, and synaptic analyses divide EPL-INs into distinct subtypes and reveal that parvalbumin-expressing fast-spiking EPL-INs (FSIs) perisomatically innervate MTCs with release-competent dendrites and synaptically detonate to mediate fast, short-latency recurrent and lateral inhibition. Sparse MTC synchronization supralinearly increases this high-fidelity inhibition, while sensory afferent activation combined with single-cell silencing reveals that individual FSIs account for a substantial fraction of total network-driven MTC lateral inhibition. OB output is thus powerfully shaped by detonation-driven high-fidelity perisomatic inhibition.

Lateralized Decrease of Parvalbumin+ Cells in the Somatosensory Cortex of ASD Models Is Correlated with Unilateral Tactile Hypersensitivity.

Inhibitory control of excitatory networks contributes to cortical functions. Increasing evidence indicates that parvalbumin (PV+)-expressing basket cells (BCs) are a major player in maintaining the balance between excitation (E) and inhibition (I). Disruption of E/I balance in cortical networks is believed to be a hallmark of autism spectrum disorder (ASD). Here, we report a lateralized decrease in the number of PV+ BCs in L2/3 of the somatosensory cortex in the dominant hemisphere of Shank3-/- and Cntnap2-/- mouse models of ASD. The dominant hemisphere was identified during a reaching task to establish each animal's dominant forepaw. Double labeling with anti-PV antibody and a biotinylated lectin (Vicia villosa lectin [VVA]) showed that the number of BCs was not different but rather, some BCs did not express PV (PV-), resulting in an elevated number of PV- VVA+ BCs. Finally, we showed that dominant hindpaws had higher mechanical sensitivity when compared with the other hindpaws. This mechanical hypersensitivity in the dominant paw strongly correlated with the decrease in the number of PV+ interneurons and reduced PV expression in the corresponding cortex. Together, these results suggest that the hypersensitivity in ASD patients could be due to decreased inhibitory inputs to the dominant somatosensory cortex.

Cell and circuit origins of fast network oscillations in the mammalian main olfactory bulb.

Neural synchrony generates fast network oscillations throughout the brain, including the main olfactory bulb (MOB), the first processing station of the olfactory system. Identifying the mechanisms synchronizing neurons in the MOB will be key to understanding how network oscillations support the coding of a high-dimensional sensory space. Here, using paired recordings and optogenetic activation of glomerular sensory inputs in MOB slices, we uncovered profound differences in principal mitral cell (MC) vs. tufted cell (TC) spike-time synchrony: TCs robustly synchronized across fast- and slow-gamma frequencies, while MC synchrony was weaker and concentrated in slow-gamma frequencies. Synchrony among both cell types was enhanced by shared glomerular input but was independent of intraglomerular lateral excitation. Cell-type differences in synchrony could also not be traced to any difference in the synchronization of synaptic inhibition. Instead, greater TC than MC synchrony paralleled the more periodic firing among resonant TCs than MCs and emerged in patterns consistent with densely synchronous network oscillations. Collectively, our results thus reveal a mechanism for parallel processing of sensory information in the MOB via differential TC vs. MC synchrony, and further contrast mechanisms driving fast network oscillations in the MOB from those driving the sparse synchronization of irregularly firing principal cells throughout cortex.

Olfactory navigation in the real world: Simple local search strategies for turbulent environments.

Olfaction informs animal navigation for foraging, social interaction, and threat evasion. However, turbulent flow on the spatial scales of most animal navigation leads to intermittent odor information and presents a challenge to simple gradient-ascent navigation. Here we present two strategies for iterative gradient estimation and navigation via olfactory cues in 2D space: tropotaxis, spatial concentration comparison (i.e., instantaneous comparison between lateral olfactory sensors on a navigating animal) and klinotaxis, spatiotemporal concentration comparison (i.e., comparison between two subsequent concentration samples as the animal moves through space). We then construct a hybrid model that uses klinotaxis but utilizes tropotactic information to guide its spatial sampling strategy. We find that for certain body geometries in which bilateral sensors are closely-spaced (e.g., mammalian nares), klinotaxis outperforms tropotaxis; for widely-spaced sensors (e.g., arthropod antennae), tropotaxis outperforms klinotaxis. We find that both navigation strategies perform well on smooth odor gradients and are robust against noisy gradients represented by stochastic odor models and real turbulent flow data. In some parameter regimes, the hybrid model outperforms klinotaxis alone, but not tropotaxis.

Nucleus accumbens feedforward inhibition circuit promotes cocaine self-administration.

The basolateral amygdala (BLA) sends excitatory projections to the nucleus accumbens (NAc) and regulates motivated behaviors partially by activating NAc medium spiny neurons (MSNs). Here, we characterized a feedforward inhibition circuit, through which BLA-evoked activation of NAc shell (NAcSh) MSNs was fine-tuned by GABAergic monosynaptic innervation from adjacent fast-spiking interneurons (FSIs). Specifically, BLA-to-NAcSh projections predominantly innervated NAcSh FSIs compared with MSNs and triggered action potentials in FSIs preceding BLA-mediated activation of MSNs. Due to these anatomical and temporal properties, activation of the BLA-to-NAcSh projection resulted in a rapid FSI-mediated inhibition of MSNs, timing-contingently dictating BLA-evoked activation of MSNs. Cocaine self-administration selectively and persistently up-regulated the presynaptic release probability of BLA-to-FSI synapses, entailing enhanced FSI-mediated feedforward inhibition of MSNs upon BLA activation. Experimentally enhancing the BLA-to-FSI transmission in vivo expedited the acquisition of cocaine self-administration. These results reveal a previously unidentified role of an FSI-embedded circuit in regulating NAc-based drug seeking and taking.

Prenatal and Early Postnatal Odorant Exposure Heightens Odor-Evoked Mitral Cell Responses in the Mouse Olfactory Bulb.

Early sensory experience shapes the anatomy and function of sensory circuits. In the mouse olfactory bulb (OB), prenatal and early postnatal odorant exposure through odorized food (food/odorant pairing) not only increases the volume of activated glomeruli but also increases the number of mitral and tufted cells (M/TCs) connected to activated glomeruli. Given the importance of M/TCs in OB output and in mediating lateral inhibitory networks, increasing the number of M/TCs connected to a single glomerulus may significantly change odorant representation by increasing the total output of that glomerulus and/or by increasing the strength of lateral inhibition mediated by cells connected to the affected glomerulus. Here, we seek to understand the functional impact of this long-term odorant exposure paradigm on the population activity of mitral cells (MCs). We use viral expression of GCaMP6s to examine odor-evoked responses of MCs following prenatal and early postnatal odorant exposure to two dissimilar odorants, methyl salicylate (MS) and hexanal, which are both strong activators of glomeruli on the dorsal OB surface. Previous work suggests that odor familiarity may decrease odor-evoked MC response in rodents. However, we find that early food-based odorant exposure significantly changes MC responses in an unexpected way, resulting in broad increases in the amplitude, number, and reliability of excitatory MC responses across the dorsal OB.

Layer- and cell type-selective co-transmission by a basal forebrain cholinergic projection to the olfactory bulb.

Cholinergic neurons in the basal forebrain project heavily to the main olfactory bulb, the first processing station in the olfactory pathway. The projections innervate multiple layers of the main olfactory bulb and strongly influence odor discrimination, detection, and learning. The precise underlying circuitry of this cholinergic input to the main olfactory bulb remains unclear, however. Here, we identify a specific basal forebrain cholinergic projection that innervates select neurons concentrated in the internal plexiform layer of the main olfactory bulb. Optogenetic activation of this projection elicits monosynaptic nicotinic and GABAergic currents in glomerular layer-projecting interneurons. Additionally, we show that the projection co-expresses markers for GABAergic neurotransmission. The data thus implicate neurotransmitter co-transmission in the basal forebrain regulation of this inhibitory olfactory microcircuit.Cholinergic neurons innervate multiple layers in the main olfactory bulb but the precise circuitry of this input is not known. Here the authors show that VGLUT3+ cholinergic neurons selectively innervate deep short axon cells in specific layers and elicit robust monosynaptic GABAergic and nicotinic postsynaptic currents.

Olfactory Bulb Deep Short-Axon Cells Mediate Widespread Inhibition of Tufted Cell Apical Dendrites.

In the main olfactory bulb (MOB), the first station of sensory processing in the olfactory system, GABAergic interneuron signaling shapes principal neuron activity to regulate olfaction. However, a lack of known selective markers for MOB interneurons has strongly impeded cell-type-selective investigation of interneuron function. Here, we identify the first selective marker of glomerular layer-projecting deep short-axon cells (GL-dSACs) and investigate systematically the structure, abundance, intrinsic physiology, feedforward sensory input, neuromodulation, synaptic output, and functional role of GL-dSACs in the mouse MOB circuit. GL-dSACs are located in the internal plexiform layer, where they integrate centrifugal cholinergic input with highly convergent feedforward sensory input. GL-dSAC axons arborize extensively across the glomerular layer to provide highly divergent yet selective output onto interneurons and principal tufted cells. GL-dSACs are thus capable of shifting the balance of principal tufted versus mitral cell activity across large expanses of the MOB in response to diverse sensory and top-down neuromodulatory input. SIGNIFICANCE STATEMENT: The identification of cell-type-selective molecular markers has fostered tremendous insight into how distinct interneurons shape sensory processing and behavior. In the main olfactory bulb (MOB), inhibitory circuits regulate the activity of principal cells precisely to drive olfactory-guided behavior. However, selective markers for MOB interneurons remain largely unknown, limiting mechanistic understanding of olfaction. Here, we identify the first selective marker of a novel population of deep short-axon cell interneurons with superficial axonal projections to the sensory input layer of the MOB. Using this marker, together with immunohistochemistry, acute slice electrophysiology, and optogenetic circuit mapping, we reveal that this novel interneuron population integrates centrifugal cholinergic input with broadly tuned feedforward sensory input to modulate principal cell activity selectively.

Early Odorant Exposure Increases the Number of Mitral and Tufted Cells Associated with a Single Glomerulus.

The highly specific organization of the olfactory bulb (OB) is well known, but the impact of early odorant experience on its circuit structure is unclear. Olfactory sensory neurons (OSNs) project axons from the olfactory epithelium to the OB, where they form spherical neuropil structures called glomeruli. These glomeruli and the postsynaptic targets of OSNs, including mitral and tufted cells (M/TCs) and juxtaglomerular cells, form glomerular modules, which represent the basic odor-coding units of the OB. Here, we labeled M/TCs within a single glomerular module of the mouse OB and show that odorant exposure that starts prenatally and continues through postnatal day 25 has a major impact on the structure of the glomerular module. We confirm that exposure increases the volume of the activated glomeruli and show that exposure increases M/TC number by >40% in a glomerulus-specific fashion. Given the role of M/TCs in OB output and in lateral inhibition, increasing the number of M/TCs connected to a single glomerulus may also increase the influence of that glomerulus on the OB network and on OB output. Our results show that early odorant exposure has a profound effect on OB connectivity and thus may affect odorant processing significantly. SIGNIFICANCE STATEMENT: Experience shapes neural circuits in a variety of ways, most commonly by changing the strength of activated connections. Relatively little is known about how experience changes circuitry in the olfactory system. Here, we show that for a genetically identified glomerulus in the mouse olfactory bulb, early odorant exposure increases the number of associated mitral and tufted cells by 40% and 100%, respectively. Understanding the structural changes induced by early odorant experience can provide insight into how bulbar organization gives rise to efficient processing. We find that odorant experience increases the number of projection neurons associated with a single glomerulus significantly, a dramatic and long-lasting structural change that may have important functional implications.

Establishing a Statistical Link between Network Oscillations and Neural Synchrony.

Pairs of active neurons frequently fire action potentials or "spikes" nearly synchronously (i.e., within 5 ms of each other). This spike synchrony may occur by chance, based solely on the neurons' fluctuating firing patterns, or it may occur too frequently to be explicable by chance alone. When spike synchrony above chances levels is present, it may subserve computation for a specific cognitive process, or it could be an irrelevant byproduct of such computation. Either way, spike synchrony is a feature of neural data that should be explained. A point process regression framework has been developed previously for this purpose, using generalized linear models (GLMs). In this framework, the observed number of synchronous spikes is compared to the number predicted by chance under varying assumptions about the factors that affect each of the individual neuron's firing-rate functions. An important possible source of spike synchrony is network-wide oscillations, which may provide an essential mechanism of network information flow. To establish the statistical link between spike synchrony and network-wide oscillations, we have integrated oscillatory field potentials into our point process regression framework. We first extended a previously-published model of spike-field association and showed that we could recover phase relationships between oscillatory field potentials and firing rates. We then used this new framework to demonstrate the statistical relationship between oscillatory field potentials and spike synchrony in: 1) simulated neurons, 2) in vitro recordings of hippocampal CA1 pyramidal cells, and 3) in vivo recordings of neocortical V4 neurons. Our results provide a rigorous method for establishing a statistical link between network oscillations and neural synchrony.

Rapid Feedforward Inhibition and Asynchronous Excitation Regulate Granule Cell Activity in the Mammalian Main Olfactory Bulb.

Granule cell-mediated inhibition is critical to patterning principal neuron activity in the olfactory bulb, and perturbation of synaptic input to granule cells significantly alters olfactory-guided behavior. Despite the critical role of granule cells in olfaction, little is known about how sensory input recruits granule cells. Here, we combined whole-cell patch-clamp electrophysiology in acute mouse olfactory bulb slices with biophysical multicompartmental modeling to investigate the synaptic basis of granule cell recruitment. Physiological activation of sensory afferents within single glomeruli evoked diverse modes of granule cell activity, including subthreshold depolarization, spikelets, and suprathreshold responses with widely distributed spike latencies. The generation of these diverse activity modes depended, in part, on the asynchronous time course of synaptic excitation onto granule cells, which lasted several hundred milliseconds. In addition to asynchronous excitation, each granule cell also received synchronous feedforward inhibition. This inhibition targeted both proximal somatodendritic and distal apical dendritic domains of granule cells, was reliably recruited across sniff rhythms, and scaled in strength with excitation as more glomeruli were activated. Feedforward inhibition onto granule cells originated from deep short-axon cells, which responded to glomerular activation with highly reliable, short-latency firing consistent with tufted cell-mediated excitation. Simulations showed that feedforward inhibition interacts with asynchronous excitation to broaden granule cell spike latency distributions and significantly attenuates granule cell depolarization within local subcellular compartments. Collectively, our results thus identify feedforward inhibition onto granule cells as a core feature of olfactory bulb circuitry and establish asynchronous excitation and feedforward inhibition as critical regulators of granule cell activity. SIGNIFICANCE STATEMENT: Inhibitory granule cells are involved critically in shaping odor-evoked principal neuron activity in the mammalian olfactory bulb, yet little is known about how sensory input activates granule cells. Here, we show that sensory input to the olfactory bulb evokes a barrage of asynchronous synaptic excitation and highly reliable, short-latency synaptic inhibition onto granule cells via a disynaptic feedforward inhibitory circuit involving deep short-axon cells. Feedforward inhibition attenuates local depolarization within granule cell dendritic branches, interacts with asynchronous excitation to suppress granule cell spike-timing precision, and scales in strength with excitation across different levels of sensory input to normalize granule cell firing rates.

Postnatal development attunes olfactory bulb mitral cells to high-frequency signaling.

Mitral cells (MCs) are a major class of principal neurons in the vertebrate olfactory bulb, conveying odor-evoked activity from the peripheral sensory neurons to olfactory cortex. Previous work has described the development of MC morphology and connectivity during the first few weeks of postnatal development. However, little is known about the postnatal development of MC intrinsic biophysical properties. To understand stimulus encoding in the developing olfactory bulb, we have therefore examined the development of MC intrinsic biophysical properties in acute slices from postnatal day (P)7-P35 mice. Across development, we observed systematic changes in passive membrane properties and action potential waveforms consistent with a developmental increase in sodium and potassium conductances. We further observed developmental decreases in hyperpolarization-evoked membrane potential sag and firing regularity, extending recent links between MC sag heterogeneity and firing patterns. We then applied a novel combination of statistical analyses to examine how the evolution of these intrinsic biophysical properties specifically influenced the representation of fluctuating stimuli by MCs. We found that immature MCs responded to frozen fluctuating stimuli with lower firing rates, lower spike-time reliability, and lower between-cell spike-time correlations than more mature MCs. Analysis of spike-triggered averages revealed that these changes in spike timing were driven by a developmental shift from broad integration of inputs to more selective detection of coincident inputs. Consistent with this shift, generalized linear model fits to MC firing responses demonstrated an enhanced encoding of high-frequency stimulus features by mature MCs.

An Empirical Model for Reliable Spiking Activity.

Understanding a neuron's transfer function, which relates a neuron's inputs to its outputs, is essential for understanding the computational role of single neurons. Recently, statistical models, based on point processes and using generalized linear model (GLM) technology, have been widely applied to predict dynamic neuronal transfer functions. However, the standard version of these models fails to capture important features of neural activity, such as responses to stimuli that elicit highly reliable trial-to-trial spiking. Here, we consider a generalization of the usual GLM that incorporates nonlinearity by modeling reliable and nonreliable spikes as being generated by distinct stimulus features. We develop and apply these models to spike trains from olfactory bulb mitral cells recorded in vitro. We find that spike generation in these neurons is better modeled when reliable and unreliable spikes are considered separately and that this effect is most pronounced for neurons with a large number of both reliable and unreliable spikes.

Brain-wide analysis of electrophysiological diversity yields novel categorization of mammalian neuron types.

For decades, neurophysiologists have characterized the biophysical properties of a rich diversity of neuron types. However, identifying common features and computational roles shared across neuron types is made more difficult by inconsistent conventions for collecting and reporting biophysical data. Here, we leverage NeuroElectro, a literature-based database of electrophysiological properties (www.neuroelectro.org), to better understand neuronal diversity, both within and across neuron types, and the confounding influences of methodological variability. We show that experimental conditions (e.g., electrode types, recording temperatures, or animal age) can explain a substantial degree of the literature-reported biophysical variability observed within a neuron type. Critically, accounting for experimental metadata enables massive cross-study data normalization and reveals that electrophysiological data are far more reproducible across laboratories than previously appreciated. Using this normalized dataset, we find that neuron types throughout the brain cluster by biophysical properties into six to nine superclasses. These classes include intuitive clusters, such as fast-spiking basket cells, as well as previously unrecognized clusters, including a novel class of cortical and olfactory bulb interneurons that exhibit persistent activity at theta-band frequencies.

Disrupting information coding via block of 4-AP-sensitive potassium channels.

Recent interest has emerged on the role of intrinsic biophysical diversity in neuronal coding. An important question in neurophysiology is understanding which voltage-gated ion channels are responsible for this diversity and how variable expression or activity of one class of ion channels across neurons of a single type affects they way populations carry information. In mitral cells in the olfactory bulb of mice, we found that biophysical diversity was conferred in part by 4-aminopyridine (4-AP)-sensitive potassium channels and reduced following block of those channels. When populations of mitral cells were stimulated with identical inputs, the diversity exhibited in their output spike patterns reduced with the addition of 4-AP, decreasing the stimulus information carried by ensembles of 15 neurons from 437 ± 15 to 397 ± 19 bits/s. Decreases in information were due to reduction in the diversity of population spike patterns generated in response to different features of the stimulus, suggesting that the coding capacity of a population can be altered by changes in the function of single ion channel types.

NeuroElectro: a window to the world's neuron electrophysiology data.

The behavior of neural circuits is determined largely by the electrophysiological properties of the neurons they contain. Understanding the relationships of these properties requires the ability to first identify and catalog each property. However, information about such properties is largely locked away in decades of closed-access journal articles with heterogeneous conventions for reporting results, making it difficult to utilize the underlying data. We solve this problem through the NeuroElectro project: a Python library, RESTful API, and web application (at http://neuroelectro.org) for the extraction, visualization, and summarization of published data on neurons' electrophysiological properties. Information is organized both by neuron type (using neuron definitions provided by NeuroLex) and by electrophysiological property (using a newly developed ontology). We describe the techniques and challenges associated with the automated extraction of tabular electrophysiological data and methodological metadata from journal articles. We further discuss strategies for how to best combine, normalize and organize data across these heterogeneous sources. NeuroElectro is a valuable resource for experimental physiologists attempting to supplement their own data, for computational modelers looking to constrain their model parameters, and for theoreticians searching for undiscovered relationships among neurons and their properties.

Greater excitability and firing irregularity of tufted cells underlies distinct afferent-evoked activity of olfactory bulb mitral and tufted cells.

Mitral and tufted cells, the two classes of principal neurons in the mammalian main olfactory bulb, exhibit morphological differences but remain widely viewed as functionally equivalent. Results from several recent studies, however, suggest that these two cell classes may encode complementary olfactory information in their distinct patterns of afferent-evoked activity. To understand how these differences in activity arise, we have performed the first systematic comparison of synaptic and intrinsic properties between mitral and tufted cells. Consistent with previous studies, we found that tufted cells fire with higher probability and rates and shorter latencies than mitral cells in response to physiological afferent stimulation. This stronger response of tufted cells could be partially attributed to synaptic differences, as tufted cells received stronger afferent-evoked excitation than mitral cells. However, differences in intrinsic excitability also contributed to the differences between mitral and tufted cell activity. Compared to mitral cells, tufted cells exhibited twofold greater excitability and peak instantaneous firing rates. These differences in excitability probably arise from differential expression of voltage-gated potassium currents, as tufted cells exhibited faster action potential repolarization and afterhyperpolarizations than mitral cells. Surprisingly, mitral and tufted cells also showed firing mode differences. While both cell classes exhibited regular firing and irregular stuttering of action potential clusters, tufted cells demonstrated a greater propensity to stutter than mitral cells. Collectively, stronger afferent-evoked excitation, greater intrinsic excitability and more irregular firing in tufted cells can combine to drive distinct responses of mitral and tufted cells to afferent-evoked input.

Origins of correlated spiking in the mammalian olfactory bulb.

Mitral/tufted (M/T) cells of the main olfactory bulb transmit odorant information to higher brain structures. The relative timing of action potentials across M/T cells has been proposed to encode this information and to be critical for the activation of downstream neurons. Using ensemble recordings from the mouse olfactory bulb in vivo, we measured how correlations between cells are shaped by stimulus (odor) identity, common respiratory drive, and other cells' activity. The shared respiration cycle is the largest source of correlated firing, but even after accounting for all observable factors a residual positive noise correlation was observed. Noise correlation was maximal on a ∼100-ms timescale and was seen only in cells separated by <200 µm. This correlation is explained primarily by common activity in groups of nearby cells. Thus, M/T-cell correlation principally reflects respiratory modulation and sparse, local network connectivity, with odor identity accounting for a minor component.

Impact of neuronal heterogeneity on correlated colored noise-induced synchronization.

Synchronization plays an important role in neural signal processing and transmission. Many hypotheses have been proposed to explain the origin of neural synchronization. In recent years, correlated noise-induced synchronization has received support from many theoretical and experimental studies. However, many of these prior studies have assumed that neurons have identical biophysical properties and that their inputs are well modeled by white noise. In this context, we use colored noise to induce synchronization between oscillators with heterogeneity in both phase-response curves and frequencies. In the low noise limit, we derive novel analytical theory showing that the time constant of colored noise influences correlated noise-induced synchronization and that oscillator heterogeneity can limit synchronization. Surprisingly, however, heterogeneous oscillators may synchronize better than homogeneous oscillators given low input correlations. We also find resonance of oscillator synchronization to colored noise inputs when firing frequencies diverge. Collectively, these results prove robust for both relatively high noise regimes and when applied to biophysically realistic spiking neuron models, and further match experimental recordings from acute brain slices.