Within the olfactory system, information flow from periphery onto output mitral cells (MCs) of bulb (OB) has been thought to be mediated by direct synaptic inputs sensory neurons (OSNs). Here, we performed patch-clamp measurements in rat and mouse OB slices investigate mechanisms OSN signaling MCs, including assumption a path, using electrical optogenetic stimulation methods that selectively activated OSNs. We found MCs are fact not typically instead require multistep, diffuse mechanism...

Natural environments feature mixtures of odorants diverse quantities, qualities and complexities. Olfactory receptor neurons (ORNs) are the first layer in sensory pathway transmit olfactory signal to higher regions brain. Yet, response ORNs is strongly non-additive, exhibits antagonistic interactions among odorants. Here, we model processing by mammalian ORNs, focusing on role inhibitory mechanisms. We show how antagonism leads an effective 'normalization' ensemble ORN response, that is,...

Abstract Sensory systems are organized hierarchically, but feedback projections frequently disrupt this order. In the olfactory bulb (OB), cortical numerically match sensory inputs. To unravel information carried by these two streams, we imaged activity of neurons (OSNs) and axons in mouse OB using calcium indicators, multiphoton microscopy, diverse stimuli. Here, show that odorant mixtures increasing complexity evoke progressively denser OSN activity, yet is similar sparsity for all Also,...

Odor cues in nature are sparse and highly fluctuating due to turbulent transport. To investigate how animals perceive these intermittent cues, we developed a behavioral task which head-restrained mice made binary decisions based on the total number of discrete odor pulses presented stochastically over several seconds. Mice readily learned this task, their performance was well-described by widely used decision models. Logistic regression choices against timing within respiratory cycle...

Abstract Odor landscapes contain complex blends of molecules that each activate unique, overlapping populations olfactory sensory neurons (OSNs). Despite the presence hundreds OSN subtypes in many animals, nature odor inputs may lead to saturation neural responses at early stages stimulus encoding. Information loss due could be mitigated by normalizing mechanisms such as antagonism level receptor-ligand interactions, whose existence and prevalence remains uncertain. By imaging axon terminals...

Methyl-CpG binding protein 2 (MeCP2) is highly expressed in neurons the vertebrate brain, and mutations of gene encoding MeCP2 cause neurodevelopmental disorder Rett syndrome. This study examines role development function thalamic GABAergic circuits. Whole cell recordings were carried out excitatory ventrobasal complex (VB) thalamus inhibitory reticular nucleus (RTN) acute brain slices from mice aged P6 through P23. At P14–P16, number quantal events was decreased VB but increased RTN...

Abstract Inputs from olfactory sensory neuron (OSN) axons expressing the same type of odorant receptor (OR) converge in glomerulus main bulb. A key marker mature OSNs is protein (OMP), whose deletion has been associated with deficits OSN signal transduction and odor discrimination. Here, we investigate glomerular responses anatomical architecture mice which one or both alleles OMP are replaced by fluorescent synaptic activity reporter, synaptopHluorin. Functionally heterogeneous glomeruli,...

Sensory systems must perform the dual and opposing tasks of being sensitive to weak stimuli while also maintaining information content in dense variable sensory landscapes. This occurs olfactory system, where OSNs are highly low concentrations odors maintain discriminability complex odor environments. How neurons (OSNs) both sensitivity sparsity is poorly understood. Here, we investigated whether calcium-activated chloride channel, TMEM16B, may support these roles male female mice. We used...

The calcium-activated chloride channel anoctamin-2 (Ano2) is thought to amplify transduction currents in olfactory receptor neurons (ORNs), a hypothesis supported by previous studies dissociated from Ano2-/- mice. Paradoxically, despite reduction ORNs, their spike output for odor stimuli may be higher. We examined the role of Ano2 ORNs native environment freely breathing mice imaging activity ORN axons as they arrive bulb glomeruli. Odor-evoked responses animals were consistently larger...

Increasing evidence indicates that the neural circuitry within glomeruli of olfactory bulb plays a major role in affecting information flow between sensory neurons (OSNs) and output mitral cells (MCs). Glutamatergic external tufted (ET) cells, located at glomeruli, can act as intermediary excitation OSNs MCs, whereas activation MCs by is, turn, suppressed inhibitory synapses onto ET cells. In this study, we used patch-clamp recordings rat slices to examine function metabotropic glutamate...

Infantile neuronal ceroid lipofuscinosis (CLN1 Batten Disease) is a devastating pediatric lysosomal storage disease caused by pathogenic variants in the CLN1 gene, which encodes depalmitoylation enzyme, palmitoyl-protein thioesterase 1 (PPT1). patients present with visual deterioration, psychomotor dysfunction, and recurrent seizures until neurodegeneration results death, typically before fifteen years of age. Histopathological features include aggregation autofluorescent material (AFSM), as...

Abstract Glutamatergic transmission in the brain typically occurs at well-defined synaptic connections, but increasing evidence indicates that neural excitation can also occur through activation of “extrasynaptic” glutamate receptors. Here, we investigated underlying mechanisms and functional properties extrasynaptic signals are part a feedforward path information flow olfactory bulb. This pathway involves glutamatergic interneurons, external tufted cells (eTCs), excited by sensory neurons...

Abstract Within a single sniff, the mammalian olfactory system can decode identity and concentration of odorants wafted on turbulent plumes air. Yet, it must do so given access only to noisy, dimensionally-reduced representation odor world provided by receptor neurons. As result, solve compressed sensing problem, relying fact that handful millions possible are present in scene. Inspired this principle, past works have proposed normative models for decoding. However, these not captured unique...

Abstract Infantile neuronal ceroid lipofuscinosis (CLN1 Batten Disease) is a devastating pediatric lysosomal storage disease caused by pathogenic variants in the CLN1 gene, which encodes depalmitoylation enzyme, palmitoyl-protein thioesterase 1 (PPT1). patients present with visual deterioration, psychomotor dysfunction, and recurrent seizures until neurodegeneration results death, typically before fifteen years of age. Histopathological features include aggregation autofluorescent material...

The sensory modalities are anatomically, biochemically and physiologically organized to detect perceive vanishingly small quantities of environmental stimulus energies. visual system's sensitivity is sufficient single photons, while in the olfactory system, odorants can be detected range parts per billion. To achieve such sensitivity, both systems have evolved biochemical amplifiers their respective transduction currents. Olfactory begins when volatilized odorant molecules bind receptor (OR)...

GABAergic periglomerular (PG) cells in the olfactory bulb are proposed to mediate an intraglomerular 'high-pass' filter through inhibition targeted onto a glomerulus. With this mechanism, weak stimuli (e.g. odour with low affinity for odourant receptor) mainly produce PG cell-driven but strong generate enough excitation overcome inhibition. may be particularly susceptible being activated by due their intrinsically small size and high input resistance. Here, we used dual-cell patch-clamp...

Abstract Odor landscapes contain complex blends of discrete molecules that each activate unique, overlapping populations olfactory sensory neurons (OSNs). Despite the presence hundreds OSN subtypes in many animals, nature odor inputs may lead to saturation neural responses at early stages stimulus encoding. Information loss due could be mitigated by normalizing mechanisms such as antagonism level receptor-ligand interactions, whose existence and prevalence remains uncertain. By imaging axon...

Olfactory sensory neurons are found deep within the nasal cavity at a spatially restricted sheet of epithelium. Due to their location behind turbinates, accessing these cells for physiological measurements in living animals is challenging, and until recently, not possible. As further complication, damage overlying bone on dorsal surface snout disrupts negative pressure distribution throughout cavities, which fundamentally alters how odorants delivered epithelium inherent mechanosensory...

Abstract Natural environments feature mixtures of odorants diverse quantities, qualities and complexities. Olfactory receptor neurons (ORNs) are the first layer in sensory pathway transmit olfactory signal to higher regions brain. Yet, response ORNs is strongly non-additive, exhibits antagonistic interactions among odorants. Here, we model processing by mammalian ORNs, focusing on role inhibitory mechanisms. Theoretically predicted curves capture experimentally determined glomerular...

Abstract Sensory systems must perform the dual and opposing tasks of being sensitive to weak stimuli while also maintaining information content in dense variable sensory landscapes. This occurs olfactory system, where OSNs are highly low concentrations odors maintain discriminability complex odor environments. How neurons (OSNs) both sensitivity sparsity is not well understood. Here, we investigated whether calcium-activated chloride channel, TMEM16B, may support these roles OSNs. We used...

Abstract Sensory systems are organized hierarchically, but feedback projections frequently disrupt this order. In the olfactory bulb (OB), cortical numerically match sensory inputs. To unravel information carried by these two streams, we imaged activity of neurons (OSNs) and axons in mouse OB using calcium indicators, multiphoton microscopy, diverse stimuli. Odorant mixtures increasing complexity evoked progressively denser OSN activity, yet was similar sparsity for all Representations...

Abstract The local circuitry within olfactory bulb (OB) glomeruli filters, transforms, and facilitates information transfer from sensory neurons to output neurons. Two key elements of this circuit are glutamatergic tufted cells (TCs) GABAergic periglomerular (PG) cells, both which actively shape mitral cell activity output. A subtype TCs, the external TCs (eTCs), can synaptically excite PG but there unresolved questions about other aspects glomerular connections, including extent...

Abstract The calcium-activated chloride channel anoctamin-2 (Ano2) is thought to amplify transduction currents in ORNs, a hypothesis supported by previous studies dissociated neurons from Ano2 -/- mice. Paradoxically, despite reduction their spike output for odor stimuli may be higher. We examined the role of ORNs native environment freely breathing mice imaging activity ORN axons as they arrive olfactory bulb glomeruli. Odor-evoked responses were consistently larger variety odorants and...