Hideki Kashiwadani

state-dependent sensory gating in olfactory cortex

Sensory systems show behavioral state-dependent gating of information flow that largely depends on the thalamus. Here we examined whether the state-dependent gating occurs in the central olfactory pathway that lacks a thalamic relay. In urethane-anesthetized rats, neocortical EEG showed a periodical alternation between two states: a slow-wave state (SWS) characterized by large and slow waves and a fast-wave state (FWS) characterized by faster waves. Single-unit recordings from olfactory cortex neurons showed robust spike responses to adequate odorants during FWS, whereas they showed only weak responses during SWS. The state-dependent change in odorant-evoked responses was observed in a majority of olfactory cortex neurons, but in only a small percentage of olfactory bulb neurons. These findings demonstrate a powerful state-dependent gating of odor information in the olfactory cortex that works in synchrony with the gating of other sensory systems. They suggest a state-dependent switchover of signal processing modes in the olfactory cortex.

Behavioral State Regulation of Dendrodendritic Synaptic Inhibition in the Olfactory Bulb

Behavioral states regulate how information is processed in local neuronal circuits. Here, we asked whether dendrodendritic synaptic interactions in the olfactory bulb vary with brain and behavioral states. To examine the state-dependent change of the dendrodendritic synaptic transmission, we monitored changes in field potential responses in the olfactory bulb of urethane-anesthetized and freely behaving rats. In urethane-anesthetized rats, granule-to-mitral dendrodendritic synaptic inhibition was larger and longer when slow waves were present in the electroencephalogram (slow-wave state) than during the fast-wave state. The state-dependent alternating change in the granule-to-mitral inhibition was regulated by the cholinergic system. In addition, the frequency of the spontaneous oscillatory activity of local field potentials and periodic discharges of mitral cells in the olfactory bulb shifted in synchrony with shifts in the neocortical brain state. Freely behaving rats showed multilevel changes in dendrodendritic synaptic inhibition that corresponded to diverse behavioral states; the inhibition was the largest during slow-wave sleep state, and successively smaller during light sleep, awake immobility, and awake moving states. These results provide evidence that behavioral state-dependent global changes in cholinergic tone modulate dendrodendritic synaptic inhibition and the information processing mode in the olfactory bulb.

Neurons in the anterior olfactory nucleus pars externa detect right or left localization of odor sources

Rodents can localize odor sources by comparing odor inputs to the right and left nostrils. However, the neuronal circuits underlying such odor localization are not known. We recorded neurons in the anterior olfactory nucleus (AON) while administering odors to the ipsilateral or contralateral (ipsi- or contra-) nostril. Neurons in the AON pars externa (AONpE) showed respiration phase-locked excitatory spike responses to ipsinostril-only stimulation with a category of odorants, and inhibitory responses to contranostril-only stimulation with the same odorants. Simultaneous odor stimulation of the ipsi- and contranostrils elicited significantly smaller responses than ipsinostril-only stimulation, indicating that AONpE neurons subtract the contranostril odor inputs from ipsinostril odor inputs. An ipsilateral odor source induced larger responses than a centrally located source, whereas an odor source at the contralateral position elicited inhibitory responses. These results indicate that individual AONpE neurons can distinguish the right or left position of an odor source by referencing signals from the two nostrils.

Compensatory Rapid Switching of Binasal Inputs in the Olfactory Cortex

Odors are inhaled through the nostrils into two segregated nasal passages and detected by sensory neurons in the bilateral olfactory epithelia. Airflow through the two nasal passages is usually asymmetrical because of alternating changes in nasal mucosal congestion. Here we show that neurons in the anterior olfactory nucleus (AON) of the adult rat olfactory cortex are ordinarily dominated by ipsi-nasal inputs and that binasal neurons in the AON respond to ipsilateral and contralateral nasal inputs with nearly equivalent odorant category selectivity. Deprivation of ipsilateral nasal inputs by unilateral nostril obstruction greatly enhanced the response to contralateral odor stimulation, in a reversible manner, in ∼33% of AON neurons within only several minutes. In 27% of AON neurons that showed spike responses induced by the inspiration of room air, ipsilateral nasal obstruction initially suppressed respiration phase-locked spike discharges and, several minutes later, induced respiration phase-locked discharges with longer delays between inspiration and response. Recordings from AON neurons in rats with anterior commissure (AC) transection indicated that the resumed respiration phase-locked discharges with longer delays were mediated by the contralateral pathway via the AC. The ipsi-nasal occlusion-induced switching of nasal inputs to individual AON neurons shows that a subset of AON neurons in the adult rat has neuronal mechanisms for rapid nostril dominance plasticity, which may enable both right and left olfactory cortices to preserve their responsiveness to the external odor world, despite reciprocal changes in nasal airflow.

Odor-Induced Persistent Discharge of Mitral Cells in the Mouse Olfactory Bulb

Short-term retention of sensory information in the form of persistent activity of central neurons plays a key role in transforming a brief sensory stimulation into longer-lasting brain responses. The olfactory system uses this transformation for various functional purposes, but the underlying neuronal mechanisms remain elusive. Here, we recorded odor-evoked, single-unit spike responses of mitral and tufted (M/T) cells in the mouse olfactory bulb (OB) under urethane anesthesia and examined the neuronal mechanisms of the persistent discharge (PD) of M/T cells that outlasts the odor stimulus for tens of seconds. The properties of the persistent afterdischarge that occurred after odor stimulation were distinct from those of odor-induced immediate spike responses in terms of the magnitude, odorant specificity, and odorant concentration-response relationship. This suggests that neuronal mechanisms other than prolonged input from olfactory sensory neurons are involved in generating these afterdischarges. Metabotropic glutamate receptor 1 (mGluR1) is expressed in the dendrites of M/T cells and is thought to participate in intraglomerular interactions among M/T cells. In OBs lacking mGluR1, or treated locally with an mGluR1-selective antagonist, the duration of the odor-induced spike responses was significantly lower than that in control OBs, indicating that mGluR1 within the bulbar neuronal circuits participates in the PD generation. These results suggest that neuronal circuits in the OB can actively prolong the odor-induced spike activity of bulbar output neurons and thus transform a brief odor input into longer-lasting activity in the central olfactory system.

Two types of olfactory cortex neurons with different signal processing mode during slow wave state

In the mouse olfactory system, each olfactory sensory neuron (OSN) expresses one functional odorant receptor (OR) gene. Furthermore, OSNs expressing the same OR species converge their axons to a specific pair of glomeruli in the olfactory bulb (OB). In the OB, OSNs form synapses with mitral/tufted cells (M/T cells) within glomeruli. In order to study the possible effect of OSN input on the circuit formation with M/T cells, we focused on Semaphorin-7a (Sema-7a), whose expression levels are regulated by OR molecules. Here we report that narris-occlusion down-regulats Sema-7a expression in OSNs and delay the synapse formation with M/T cells. We also found that the Sema-7a receptor, PlexinC1 but not Integrin 1, is strongly expressed in the dendrites of M/T cells in neonatal mice. In the Sema-7a knock out, synapse formation of M/T cell dendrites with OSN axons is affected. These results suggest that Sema-7a plays an important role in the synapse formation of M/T cells in an activity-dependent manner.

Synchronized oscillatory discharges of mitral/tufted cells with overlapping molecular receptive ranges in the rabbit olfactory bulb

Individual glomeruli in the mammalian olfactory bulb receive a massive convergence of olfactory axons that originate from sensory neurons expressing the same type of odorant receptor. Thus, individual mitral/tufted (M/T) cells associated with a glomerulus respond to a range of odor molecules that may be detected by the same type of odorant receptor. In this study, we examined whether there are functional interactions between Mfl cells associated with different glomeruli and thus with different types of odorant receptor. In urethane anesthetized rabbits, spike activities were recorded simultaneously from two M/T cells located 300-500 pm apart. A cross-correlation analysis of spikes of two M/T cells that have different but overlapping molecular receptive ranges showed a synchronized oscillatory discharge pattern when stimulated with an odorant effective in activating both cells. The results suggest that synchronization of discharges of MIT cells associated with different glomeruli might contribute to the integration of signals derived from different types of odorant receptors.