Sasha Devore

Noradrenergic and cholinergic modulation of olfactory bulb sensory processing

Neuromodulation in sensory perception serves important functions such as regulation of signal to noise ratio, attention, and modulation of learning and memory. Neuromodulators in specific sensory areas often have highly similar cellular, but distinct behavioral effects. To address this issue, we here review the function and role of two neuromodulators, acetylcholine (Ach) and noradrenaline (NE) for olfactory sensory processing in the adult main olfactory bulb. We first describe specific bulbar sensory computations, review cellular effects of each modulator and then address their specific roles in bulbar sensory processing. We finally put these data in a behavioral and computational perspective.

Effects of Reverberation on the Directional Sensitivity of Auditory Neurons across the Tonotopic Axis: Influences of Interaural Time and Level Differences

In reverberant environments, acoustic reflections interfere with the direct sound arriving at a listeners ears, distorting the binaural cues for sound localization. We investigated the effects of reverberation on the directional sensitivity of single neurons in the inferior colliculus (IC) of unanesthetized rabbits. We find that reverberation degrades the directional sensitivity of single neurons, although the amount of degradation depends on the characteristic frequency (CF) and the type of binaural cues available. When interaural time differences (ITDs) are the only available directional cue, low-CF cells sensitive to ITDs in the waveform fine time structure maintain better directional sensitivity in reverberation than high-CF cells sensitive to ITDs in the envelope induced by cochlear filtering. Conversely, when both ITD and interaural level difference (ILD) cues are available, directional sensitivity in reverberation is comparable throughout the tonotopic axis of the IC. This result suggests that, at high frequencies, ILDs provide better directional information than envelope ITDs, emphasizing the importance of the ILD-processing pathway for sound localization in reverberation.

Blocking muscarinic receptors in the olfactory bulb impairs performance on an olfactory short-term memory task.

Cholinergic inputs to cortical processing networks have long been associated with attentional and top-down processing. Experimental and theoretical studies suggest that cholinergic inputs to the main olfactory bulb (OB) can modulate both neural and behavioral odor discrimination. Previous experiments from our laboratory and others demonstrate that blockade of nicotinic receptors directly impairs olfactory discrimination, whereas blockade of muscarinic receptors only measurably impairs olfactory perception when task demands are made more challenging, such as when very low-concentration odors are used or rats are required to maintain sensory memory over long durations. To further investigate the role of muscarinic signaling in the OB, we developed an olfactory delayed match-to-sample task using a digging-based behavioral paradigm. We find that rats are able to maintain robust short-term odor memory for 10–100 s. To investigate the role of muscarinic signaling in task performance, we bilaterally infused scopolamine into the OB. We find that high dosages of scopolamine (38 mM) impair performance on the task across all delays tested, including the baseline condition with no delay, whereas lower dosages (7.6 mM and 22.8 mM) had no measureable effects. These results indicate that general execution of the match-to-sample task, even with no delay, is at least partially dependent on muscarinic signaling in the OB.

Dual sensitivity of inferior colliculus neurons to ITD in the envelopes of high-frequency sounds: experimental and modeling study

Human listeners are sensitive to interaural time differences (ITDs) in the envelopes of sounds, which can serve as a cue for sound localization. Many high-frequency neurons in the mammalian inferior colliculus (IC) are sensitive to envelope-ITDs of sinusoidally amplitude-modulated (SAM) sounds. Typically, envelope-ITD-sensitive IC neurons exhibit either peak-type sensitivity, discharging maximally at the same delay across frequencies, or trough-type sensitivity, discharging minimally at the same delay across frequencies, consistent with responses observed at the primary site of binaural interaction in the medial and lateral superior olives (MSO and LSO), respectively. However, some high-frequency IC neurons exhibit dual types of envelope-ITD sensitivity in their responses to SAM tones, that is, they exhibit peak-type sensitivity at some modulation frequencies and trough-type sensitivity at other frequencies. Here we show that high-frequency IC neurons in the unanesthetized rabbit can also exhibit dual types of envelope-ITD sensitivity in their responses to SAM noise. Such complex responses to SAM stimuli could be achieved by convergent inputs from MSO and LSO onto single IC neurons. We test this hypothesis by implementing a physiologically explicit, computational model of the binaural pathway. Specifically, we examined envelope-ITD sensitivity of a simple model IC neuron that receives convergent inputs from MSO and LSO model neurons. We show that dual envelope-ITD sensitivity emerges in the IC when convergent MSO and LSO inputs are differentially tuned for modulation frequency.

Basal forebrain dynamics during nonassociative and associative olfactory learning.

Cholinergic and GABAergic projections from the horizontal diagonal band (HDB) and medial preoptic area (MCPO) of the basal forebrain to the olfactory system are associated with odor discrimination and odor learning, as well as modulation of neural responses in olfactory structures. Whereas pharmacological and lesion studies give insights into the functional role of these modulatory inputs on a slow timescale, the response dynamics of neurons in the HDB/MCPO during olfactory behaviors have not been investigated. In this study we examined how these neurons respond during two olfactory behaviors: spontaneous investigation of odorants and odor-reward association learning. We observe rich heterogeneity in the response dynamics of individual HDB/MCPO neurons, with a substantial fraction of neurons exhibiting task-related modulation. HDB/MCPO neurons show both rapid and transient responses during bouts of odor investigation and slow, long-lasting modulation of overall response rate based on behavioral demands. Specifically, baseline rates were higher during the acquisition phase of an odor-reward association than during spontaneous investigation or the recall phase of an odor reward association. Our results suggest that modulatory projections from the HDB/MCPO are poised to influence olfactory processing on multiple timescales, from hundreds of milliseconds to minutes, and are therefore capable of rapidly setting olfactory network dynamics during odor processing and learning.

Effect of Reverberation on Directional Sensitivity of Auditory Neurons: Central and Peripheral Factors

In reverberant environments, acoustic reflections interfere with the direct sound arriving at a listener’s ears, distorting the binaural cues for sound localization. Using virtual auditory space simulation techniques, we investigated the effects of reverberation on the directional rate responses of single neurons in the inferior colliculus (IC) of unanesthetized rabbits. We find that reverberation degrades the directional sensitivity of single neurons, although the amount of degradation depends on the characteristic frequency (CF) and the type of binaural cues available. To investigate the extent to which these midbrain results reflect peripheral processing of the monaural input signals, we extracted directional information from spike trains recorded from auditory nerve (AN) in anesthetized cat for the same VAS stimuli. Our results suggest that the frequency-dependent degradation in ITD-based directional sensitivity in reverberation originates in the auditory periphery.

Neural and Behavioral Sensitivities to Azimuth Degrade with Distance in Reverberant Environments

Reverberation poses a challenge to sound localization in rooms. In an anechoic space, the only energy reaching a listener’s ears arrives directly from the sound source. In reverberant environments, however, acoustic reflections interfere with the direct sound and distort the ongoing directional cues, leading to fluctuations in interaural time and level differences (ITD and ILD) over the course of the stimulus (Shinn-Cunningham et al. 2005). These effects become more severe as the distance from sound source to listener increases, which causes the ratio of direct to reverberant energy (D/R) to decrease (Hartmann et al. 2005; Shinn-Cunningham et al. 2005). Few neurophysiological and psychophysical studies have systematically examined sensitivity to sound source azimuth as a function of D/R (Rakerd and Hartmann 2005). Here we report the results of two closely-integrated studies aimed at characterizing the influence of acoustic reflections like those present in typical classrooms on both the directional sensitivity of auditory neurons and the localization performance of human listeners. We used low-frequency stimuli to emphasize ITDs, which are the most important binaural cue for sounds containing low-frequency energy (MacPherson and Middlebrooks 2002; Wightman and Kistler 1992). We find that reverberation reduces the directional sensitivity of low-frequency, ITD-sensitive neurons in the cat inferior colliculus (IC), and that this degradation becomes more severe with decreasing D/R (increasing distance). We show parallel degradations in human sensitivity to the azimuth of low-frequency noise.

The influence of reverberation on spatial release of masking in consonant identification

This study investigates how reverberation influences spatial release of masking in consonant identification. HRTFs were measured in two rooms with different reverberation characteristics from sources directly in front of and to the right of the listener at a distance of 1 m. These two sets of room HRTFs and pseudo‐anechoic HRTFs (time‐windowing out the reverberation) were used to simulate a speech target and speech‐shaped masker over headphones in two spatial configurations. In both configurations, the target was directly ahead of the listener; the masker was either directly ahead or 45° to the right of the listener. Subjects were asked to identify the initial or final consonant (one of 12 stop and fricative consonants) in CVC nonsense syllables for different target‐to‐masker levels. Each spatial configuration and room condition was tested using binaural, monaural‐left, and monaural‐right headphone presentations. Consonant confusion matrices are analyzed to determine how specific acoustic features of cons...

Internal cholinergic regulation of learning and recall in a model of olfactory processing

In the olfactory system, cholinergic modulation has been associated with contrast modulation and changes in receptive fields in the olfactory bulb, as well the learning of odor associations in olfactory cortex. Computational modeling and behavioral studies suggest that cholinergic modulation could improve sensory processing and learning while preventing pro-active interference when task demands are high. However, how sensory inputs and/or learning regulate incoming modulation has not yet been elucidated. We here use a computational model of the olfactory bulb, piriform cortex (PC) and horizontal limb of the diagonal band of Broca (HDB) to explore how olfactory learning could regulate cholinergic inputs to the system in a closed feedback loop. In our model, the novelty of an odor is reflected in firing rates and sparseness of cortical neurons in response to that odor and these firing rates can directly regulate learning in the system by modifying cholinergic inputs to the system. In the model, cholinergic neurons reduce their firing in response to familiar odors—reducing plasticity in the PC, but increase their firing in response to novel odor—increasing PC plasticity. Recordings from HDB neurons in awake behaving rats reflect predictions from the model by showing that a subset of neurons decrease their firing as an odor becomes familiar.

Dark matter of the bulb

A study now shows that granule cells deep in the olfactory bulb exhibit wildly different response dynamics depending on behavioral state, suggesting they could configure network changes across behavioral states.