Neural phase-locking to temporal fluctuations is a fundamental and unique mechanism by which acoustic information is encoded by the auditory system. The perceptual role of this metabolically expensive mechanism, the neural phase-locking to temporal fine structure (TFS) in particular, is debated. Although hypothesized, it is unclear if auditory perceptual deficits in certain clinical populations are attributable to deficits in TFS coding. Efforts to uncover the role of TFS have been impeded by the fact that there are no established assays for quantifying the fidelity of TFS coding at the individual level. While many candidates have been proposed, for an assay to be useful, it should not only intrinsically depend on TFS coding, but should also have the property that individual differences in the assay reflect TFS coding per se over and beyond other sources of variance. Here, we evaluate a range of behavioral and electroencephalogram (EEG)-based measures as candidate individualized measures of TFS sensitivity...

Abnormal levels of acoustic activity can result in hearing problems such as tinnitus and language processing disorders, but the underlying cellular and synaptic changes triggered by abnormal activity are not well understood. To address this issue, we studied the time course of activity-dependent changes that occur at auditory nerve synapses in mice of both sexes after noise exposure and conductive hearing loss. We found that EPSC amplitude and synaptic depression decreased within two days of noise exposure, through a decrease in the probability of vesicle release ( P r). This was followed by a gradual increase in EPSC amplitude, through a larger pool of releasable vesicles ( N ). Occlusion of the ear canal led to a rapid decrease in EPSC amplitude, through a decrease in N , which was followed by an increase in EPSC amplitude and synaptic depression through an increase in P r. After returning to normal sound levels, synaptic depression recovered to control levels within 1 to 2 d. However, repeated exposure ...

Hilar mossy cells regulate network function in the hippocampus through both direct excitation and di-synaptic inhibition of dentate granule cells (DGCs). Substantial mossy cell loss accompanies hippocampal circuit changes in epilepsy. We examined the contribution of surviving mossy cells to network activity in the reorganized dentate gyrus after pilocarpine-induced status epilepticus. To examine functional circuit changes, we optogenetically stimulated mossy cells in acute hippocampal slices from male mice. In control mice, activation of mossy cells produced monosynaptic excitatory and di-synaptic GABAergic currents in DGCs. In pilocarpine-treated mice, mossy cell density and excitation of DGCs were reduced in parallel, with only a minimal reduction in feedforward inhibition, enhancing the inhibition:excitation ratio. Surprisingly, mossy cell-driven excitation of parvalbumin-positive basket cells, primary mediators of feed-forward inhibition, was maintained. Our results suggest that mossy cell outputs reor...

Inhibitory microcircuits play an essential role in regulating cortical responses to sensory stimuli. Interneurons that inhibit dendritic or somatic integration act as gatekeepers for neural activity, synaptic plasticity and the formation of sensory representations. Conversely, interneurons that selectively inhibit other interneurons can open gates through disinhibition. In the anterior piriform cortex (APC), relief of inhibition permits associative long-term potentiation (LTP) of excitatory synapses between pyramidal neurons. However, the interneurons and circuits mediating disinhibition have not been elucidated. In this study, we use an optogenetic approach in mice of both sexes to identify the inhibitory interneurons and disinhibitory circuits that regulate LTP. We focused on three prominent interneuron classes- somatostatin (SST), parvalbumin (PV), and vasoactive intestinal polypeptide (VIP) interneurons. We find that LTP is gated by the inactivation SST or PV interneurons and by the activation of VIP i...

Covert spatial attention (without concurrent eye movements) improves performance in many visual tasks (e.g., orientation discrimination and visual search). However, both covert attention systems—endogenous (voluntary) and exogenous (involuntary)—exhibit differential effects on performance in tasks mediated by spatial and temporal resolution suggesting an underlying mechanistic difference. We investigated whether these differences manifest in sensory tuning by assessing whether and how endogenous and exogenous attention differentially alter the representation of two basic visual dimensions—orientation and spatial frequency (SF). The same human observers detected a grating embedded in noise in two separate experiments (with endogenous or exogenous attention cues). Reverse correlation was used to infer the underlying neural representation from behavioral responses, and we linked our results to established neural computations via a normalization model of attention. Both endogenous and exogenous attention simil...

A main characteristic of dyslexia is poor use of sound categories. We now studied within-session learning of new sound categories in dyslexia, behaviorally and neurally, using fMRI. Human participants (males and females) with and without dyslexia were asked to discriminate which of two serially-presented tones had a higher pitch. The task was administered in two protocols, with and without a repeated reference frequency. The reference condition introduces regularity, and enhances frequency sensitivity in typically developing (TD) individuals. Enhanced sensitivity facilitates the formation of “high” and “low” pitch categories above and below this reference, respectively. We found that in TDs, learning was paralleled by a gradual decrease in activation of the primary auditory cortex (PAC), and reduced activation of the superior temporal gyrus (STG) and left posterior parietal cortex (PPC), which are important for using sensory history. No such sensitivity was found among individuals with dyslexia (IDDs). Rat...

Despite numerous studies examining the mechanisms of operant conditioning (OC), the diversity of OC plasticity loci and their synergism have not been examined sufficiently. In the well-characterized feeding neural circuit of Aplysia , in vivo and in vitro appetitive OC increases neuronal excitability and electrical coupling among several neurons leading to an increase in expression of ingestive behavior. Here, we used the in vitro analog of OC to investigate whether OC reduces the excitability of a neuron, B4, whose inhibitory connections decrease expression of ingestive behavior. We found OC decreased the excitability of B4. This change appeared intrinsic to B4 because it could be replicated with an analog of OC in isolated cultures of B4 neurons. In addition to changes in B4 excitability, OC decreased the strength of B4's inhibitory connection to a key decision-making neuron, B51. The OC-induced changes were specific without affecting the excitability of another neuron critical for feeding behavior, B8, ...

The dorsal anterior cingulate cortex (dACC) plays a critical role in cognitive control over different domains of tasks. The dACC activities uniformly represent task-generic intensities of control signals across different tasks. However, it remains unclear whether the dACC activities could also encode task identities of control signals across different tasks. If so, how the two types of control information are coherently organized in the dACC? Decision uncertainty is an internally-generated control signal by retrospective monitoring, namely, metacognition, even with no external feedback. We here investigated neural representations of decision uncertainty accompanying three decision-making tasks in the domains of perception, rule-based inference, and memory using trial-by-trial univariate and multivariate analyses on functional magnetic resonance imaging (fMRI) data acquired on human male and female healthy subjects. Our results demonstrated that the dACC represented decision uncertainty commonly across the ...

There are two distinct sources of retinal image motion: objects moving in the world and observer movement. When the eyes move to track a target of interest, the retinal velocity of some object in the scene will depend on both eye velocity and that object's motion in the world. Thus, to compute the object's velocity relative to the head, a coordinate transformation must be performed by vectorially adding eye velocity and retinal velocity. In contrast, a very different interaction between retinal and eye velocity signals has been proposed to underlie estimation of depth from motion parallax, which involves computing the ratio of retinal and eye velocities. We examined how neurons in the middle temporal (MT) area of male macaques combine eye velocity and retinal velocity, to test whether this interaction is more consistent with a partial coordinate transformation (for computing head-centered object motion) or a multiplicative gain interaction (for computing depth from motion parallax). We find that some MT ne...

Amanda Jiménez-Pompa, Sara Sanz-Lázaro, Romidan Ewere Omodolor, José Medina-Polo, Carmen González-Enguita, et al. (see pages [1173–1183][1]) Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels with roles throughout the CNS and peripheral nervous system, as well as in