Low Spontaneous Firing Rates Research Articles

Molecular signatures define subtypes of auditory afferents with distinct peripheral projection patterns and physiological properties

Type I spiral ganglion neurons (SGNs) are the auditory afferents that transmit sound information from cochlear inner hair cells (IHCs) to the brainstem. These afferents consist of physiological subtypes that differ in their spontaneous firing rate (SR), activation threshold, and dynamic range and have been described as low, medium, and high SR fibers. Lately, single-cell RNA sequencing experiments have revealed three molecularly defined type I SGN subtypes. The extent to which physiological type I SGN subtypes correspond to molecularly defined subtypes is unclear. To address this question, we have generated mouse lines expressing CreERT2 in SGN subtypes that allow for a physiological assessment of molecular subtypes. We show that Lypd1-CreERT2 expressing SGNs represent a well-defined group of neurons that preferentially innervate the IHC modiolar side and exhibit a narrow range of low SRs. In contrast, Calb2-CreERT2 expressing SGNs preferentially innervate the IHC pillar side and exhibit a wider range of SRs, thus suggesting that a strict stratification of all SGNs into three molecular subclasses is not obvious, at least not with the CreERT2 tools used here. Genetically marked neuronal subtypes refine their innervation specificity onto IHCs postnatally during the time when activity is required to refine their molecular phenotype. Type I SGNs thus consist of genetically defined subtypes with distinct physiological properties and innervation patterns. The molecular subtype-specific lines characterized here will provide important tools for investigating the role of the physiologically distinct type I SGNs in encoding sound signals.

A potential approach for reducing hearing difficulty by improving perception of intensity changes in speech

Many listeners report hearing difficulty, especially for speech in noisy environments, despite having normal audiometric thresholds. Recent work suggests that such cases may be caused by disruptions in coding of suprathreshold sounds at early stages of auditory processing. Specifically, differences in the function of auditory nerve fibers with lower spontaneous firing rates could disrupt coding of intensity changes for sounds in the typical range used for speech communication. In turn, this could affect perception of acoustic cues in speech that are dependent on intensity changes over time, such as voice onset time (VOT). The current study investigated a speech sound manipulation designed to counteract the effects of such disruptions by making intensity differences in the signal more pronounced. Listeners heard speech sounds varying along two acoustic dimensions that provide information about word-initial voicing, VOT and f0 onset, and categorized sounds as either voiced or voiceless. Results showed that the intensity manipulation reduced listeners' use of f0 for voicing categorization and also affected their use of VOT. This suggests that intensity manipulations can make acoustic cues like VOT more salient, providing a potential treatment approach for listeners who have difficulty coding intensity differences in speech.

State-Dependent Modulation of Activity in Distinct Layer 6 Corticothalamic Neurons in Barrel Cortex of Awake Mice.

Layer 6 corticothalamic (L6 CT) neurons are in a strategic position to control sensory input to the neocortex, yet we understand very little about their functions. Apart from studying their anatomic, physiological, and synaptic properties, most recent efforts have focused on the activity-dependent influences CT cells can exert on thalamic and cortical neurons through causal optogenetic manipulations. However, few studies have attempted to study them during behavior. To address this gap, we performed juxtacellular recordings from optogenetically identified CT neurons in whisker-related primary somatosensory cortex (wS1) of awake, head-fixed mice (either sex) free to rest quietly or self-initiate bouts of whisking and locomotion. We found a rich diversity of response profiles exhibited by CT cells. Their spiking patterns were either modulated by whisking-related behavior (∼28%) or not (∼72%). Whisking-responsive neurons exhibited both increases (activated-type) and decreases in firing rates (suppressed-type) that aligned with whisking onset better than locomotion. We also encountered responsive neurons with preceding modulations in firing rate before whisking onset. Overall, whisking better explained these changes in rates than overall changes in arousal. Whisking-unresponsive CT cells were generally quiet, with many having low spontaneous firing rates (sparse-type) and others being completely silent (silent-type). Remarkably, the sparse firing CT population preferentially spiked at the state transition point when pupil diameter constricted, and the mouse entered quiet wakefulness. Thus, our results demonstrate that L6 CT cells in wS1 show diverse spiking patterns, perhaps subserving distinct functional roles related to precisely timed responses during complex behaviors and transitions between discrete waking states.SIGNIFICANCE STATEMENT Layer 6 corticothalamic neurons provide a massive input to the sensory thalamus and local connectivity within cortex, but their role in thalamocortical processing remains unclear because of difficulty accessing and isolating their activity. Although several recent optogenetic studies reveal that the net influence of corticothalamic actions, suppression versus enhancement, depends critically on the rate these neurons fire, the factors that influence their spiking are poorly understood, particularly during wakefulness. Using the well-established Ntsr1-Cre line to target this elusive population in the whisker somatosensory cortex of awake mice, we found that corticothalamic neurons show diverse state-related responses and modulations in firing rate. These results suggest separate corticothalamic populations can differentially influence thalamocortical excitability during rapid state transitions in awake, behaving animals.

Electrophysiological abnormalities in induced pluripotent stem cell-derived cardiomyocytes generated from Duchenne muscular dystrophy patients.

Duchenne muscular dystrophy (DMD) is an X‐linked progressive muscle degenerative disease, caused by mutations in the dystrophin gene and resulting in death because of respiratory or cardiac failure. To investigate the cardiac cellular manifestation of DMD, we generated induced pluripotent stem cells (iPSCs) and iPSC‐derived cardiomyocytes (iPSC‐CMs) from two DMD patients: a male and female manifesting heterozygous carrier. Dystrophin mRNA and protein expression were analysed by qRT‐PCR, RNAseq, Western blot and immunofluorescence staining. For comprehensive electrophysiological analysis, current and voltage clamp were used to record transmembrane action potentials and ion currents, respectively. Microelectrode array was used to record extracellular electrograms. X‐inactive specific transcript (XIST) and dystrophin expression analyses revealed that female iPSCs underwent X chromosome reactivation (XCR) or erosion of X chromosome inactivation, which was maintained in female iPSC‐CMs displaying mixed X chromosome expression of wild type (WT) and mutated alleles. Both DMD female and male iPSC‐CMs presented low spontaneous firing rate, arrhythmias and prolonged action potential duration. DMD female iPSC‐CMs displayed increased beat rate variability (BRV). DMD male iPSC‐CMs manifested decreased I f density, and DMD female and male iPSC‐CMs showed increased I Ca,L density. Our findings demonstrate cellular mechanisms underlying electrophysiological abnormalities and cardiac arrhythmias in DMD.

Maturation of Spontaneous Firing Properties after Hearing Onset in Rat Auditory Nerve Fibers: Spontaneous Rates, Refractoriness, and Interfiber Correlations.

The inner hair cell (IHC)/auditory nerve fiber (ANF) synapse is the first synapse of the auditory pathway. Remarkably, each IHC is the sole partner of 10-30 ANFs with a range of spontaneous firing rates (SRs). Low and high SR ANFs respond to sound differently, and both are important for encoding sound information across varying acoustical environments. Here we demonstrate SR diversification after hearing onset by afferent recordings in acutely excised rat cochlear preparations. We describe developmental changes in spike train statistics and endogenous firing in immature ANFs. Dual afferent recordings provide the first direct evidence that fibers with different SRs contact the same IHCs and do not show correlated spike timing at rest. These results lay the groundwork for understanding the differential sensitivity of ANFs to acoustic trauma.

Sex differences in cerebellar synaptic transmission and sex-specific responses to autism-linked Gabrb3 mutations in mice.

Neurons of the cerebellar nuclei (CbN) transmit cerebellar signals to premotor areas. The cerebellum expresses several autism-linked genes, including GABRB3, which encodes GABAA receptor β3 subunits and is among the maternal alleles deleted in Angelman syndrome. We tested how this Gabrb3 m-/p+ mutation affects CbN physiology in mice, separating responses of males and females. Wild-type mice showed sex differences in synaptic excitation, inhibition, and intrinsic properties. Relative to females, CbN cells of males had smaller synaptically evoked mGluR1/5-dependent currents, slower Purkinje-mediated IPSCs, and lower spontaneous firing rates, but rotarod performances were indistinguishable. In mutant CbN cells, IPSC kinetics were unchanged, but mutant males, unlike females, showed enlarged mGluR1/5 responses and accelerated spontaneous firing. These changes appear compensatory, since mutant males but not females performed indistinguishably from wild-type siblings on the rotarod task. Thus, sex differences in cerebellar physiology produce similar behavioral output, but provide distinct baselines for responses to mutations.

Leg Regrowth in Blaberus discoidalis (Discoid Cockroach) following Limb Autotomy versus Limb Severance and Relevance to Neurophysiology Experiments.

BackgroundMany insects can regenerate limbs, but less is known about the regrowth process with regard to limb injury type. As part of our neurophysiology education experiments involving the removal of a cockroach leg, 1) the ability of Blaberus discoidalis cockroaches to regenerate a metathoracic leg was examined following autotomy at the femur/trochanter joint versus severance via a transverse coxa-cut, and 2) the neurophysiology of the detached legs with regard to leg removal type was studied by measuring spike firing rate and microstimulation movement thresholds.Leg Regrowth ResultsFirst appearance of leg regrowth was after 5 weeks in the autotomy group and 12 weeks in the coxa-cut group. Moreover, regenerated legs in the autotomy group were 72% of full size on first appearance, significantly larger (p<0.05) than coxa-cut legs (29% of full size at first appearance). Regenerated legs in both groups grew in size with each subsequent molt; the autotomy-removed legs grew to full size within 18 weeks, whereas coxa-cut legs took longer than 28 weeks to regrow. Removal of the metathoracic leg in both conditions did not have an effect on mortality compared to matched controls with unmolested legs.Neurophysiology ResultsAutotomy-removed legs had lower spontaneous firing rates, similar marked increased firing rates upon tactile manipulation of tibial barbs, and a 10% higher electrical microstimulation threshold for movement.SummaryIt is recommended that neurophysiology experiments on cockroach legs remove the limb at autotomy joints instead of coxa cuts, as the leg regenerates significantly faster when autotomized and does not detract from the neurophysiology educational content.

The anterior paraventricular thalamus modulates neuronal excitability in the suprachiasmatic nuclei of the rat.

The suprachiasmatic nucleus (SCN) in mammals is the master clock which regulates circadian rhythms. Neural activity of SCN neurons is synchronized to external light through the retinohypothalamic tract (RHT). The paraventricular thalamic nucleus (PVT) is a neural structure that receives synaptic inputs from, and projects back to, the SCN. Lesioning the anterior PVT (aPVT) modifies the behavioral phase response curve induced by short pulses of bright light. In order to study the influence of the aPVT on SCN neural activity, we addressed whether the stimulation of the aPVT can modulate the electrical response of the SCN to either retinal or RHT stimulation. Using in vitro and in vivo recordings, we found a large population of SCN neurons responsive to the stimulation of either aPVT or RHT pathways. Furthermore, we found that simultaneous stimulation of the aPVT and the RHT increased neuronal responsiveness and spontaneous firing rate (SFR) in neurons with a low basal SFR (which also have more negative membrane potentials), such as quiescent and arrhythmic neurons, but no change was observed in neurons with rhythmic firing patterns and more depolarized membrane potentials. These results suggest that inputs from the aPVT could shift the membrane potential of an SCN neuron to values closer to its firing threshold and thus contribute to integration of the response of the circadian clock to light.

Individual differences in acoustic acuity at supra-threshold level

The ability to detect acoustic amplitude modulated envelopes differs even among listeners with normal hearing thresholds (NHTs), an effect that to some degree may correlate with noise exposure history. Moreover, at least one animal study suggests that auditory nerve fibers (ANFs) with lower spontaneous firing rates (high thresholds) are more vulnerable to damage from noise exposure compared to those with high spontaneous rate ANFs. Given that NHTs depend primarily on high-spontaneous rate fibers, even relatively severe loss of low-spontaneous ANFs could be present in listeners that have “normal hearing” according to traditional hearing screenings. Here, we evaluated the robustness of supra-threshold coding, which may relate to low-spontaneous ANFs health, in listeners with NHTs. Specifically, we measured the phase-locking-values (PLVs) of subcortical envelope following responses to SAM tones (carrier: 1500 Hz; modulation rate: 100 Hz) at two sensation levels (20/50 dB SL) and with two modulation depths (0/−6 dB). Results reveal huge individual differences in PLV strengths that are negatively correlated with behavioral amplitude modulation detection thresholds for noises at a moderate supra-threshold level (carrier: band-pass-filtered noise centered at 1500 Hz with 300 Hz bandwidth; modulation rate:10 Hz). Our data support the hypothesis that the number of operational low-spontaneous rate ANFs may differ human listeners with NHTs, and that deficit in low-spontaneous rate ANFs can lead to deficits in perceptual abilities.

α-Band oscillations in intracellular membrane potentials of dentate gyrus neurons in awake rodents.

The hippocampus and dentate gyrus play critical roles in processing declarative memories and spatial information. Dentate granule cells, the first relay in the trisynaptic circuit through the hippocampus, exhibit low spontaneous firing rates even during locomotion. Using intracellular recordings from dentate neurons in awake mice operating a levitated spherical treadmill, we found a transient membrane potential α-band oscillation associated with the onset of spontaneous motion, especially forward walking movements. While often subthreshold, α oscillations could regulate spike timing during locomotion and may enable dentate gyrus neurons to respond to specific cortical afferent pathways while maintaining low average firing rates.

Disruption of lateral olivocochlear neurons with a dopaminergic neurotoxin depresses spontaneous auditory nerve activity

Neurons of the lateral olivocochlear (LOC) system project from the auditory brainstem to the cochlea, where they synapse on radial dendrites of auditory nerve fibers. Selective LOC disruption depresses sound-evoked auditory nerve activity in the guinea pig, but enhances it in the mouse. Here, LOC disruption depressed spontaneous auditory nerve activity in the guinea pig. Recordings from single auditory nerve fibers revealed a significantly reduced proportion of fibers with the highest spontaneous firing rates (SRs) and an increased proportion of neurons with lower SRs. Ensemble activity, estimated using round window noise, also decreased after LOC disruption. Decreased spontaneous activity after LOC disruption may be a consequence of reduced tonic release of excitatory transmitters from the LOC terminals in guinea pigs.

Odor Processing by Adult-Born Neurons

The adult mammalian brain is continuously supplied with adult-born neurons in the olfactory bulb (OB) and hippocampus, where they are thought to be important for circuit coding and plasticity. However, direct evidence for the actual involvement of these neurons in neural processing is still lacking. We recorded the spiking activity of adult-born periglomerular neurons in the mouse OB invivo using two-photon-targeted patch recordings. We show that odor responsiveness reaches a peak during neuronal development and then recedes at maturity. Sensory enrichment during development enhances the selectivity of adult-born neurons after maturation, without affecting neighboring resident neurons. Thus, in the OB circuit, adult-born neurons functionally integrate into the circuit, where they acquire distinct response profiles in an experience-dependent manner. The constant flow of these sensitive neurons into the circuit provides it with a mechanism of long-term plasticity, wherein new neurons mature to process odor information based on past demands.

Transgenic Mouse Lines Subdivide External Segment of the Globus Pallidus (GPe) Neurons and Reveal Distinct GPe Output Pathways

Cell-type diversity in the brain enables the assembly of complex neural circuits, whose organization and patterns of activity give rise to brain function. However, the identification of distinct neuronal populations within a given brain region is often complicated by a lack of objective criteria to distinguish one neuronal population from another. In the external segment of the globus pallidus (GPe), neuronal populations have been defined using molecular, anatomical, and electrophysiological criteria, but these classification schemes are often not generalizable across preparations and lack consistency even within the same preparation. Here, we present a novel use of existing transgenic mouse lines, Lim homeobox 6 (Lhx6)-Cre and parvalbumin (PV)-Cre, to define genetically distinct cell populations in the GPe that differ molecularly, anatomically, and electrophysiologically. Lhx6-GPe neurons, which do not express PV, are concentrated in the medial portion of the GPe. They have lower spontaneous firing rates, narrower dynamic ranges, and make stronger projections to the striatum and substantia nigra pars compacta compared with PV-GPe neurons. In contrast, PV-GPe neurons are more concentrated in the lateral portions of the GPe. They have narrower action potentials, deeper afterhyperpolarizations, and make stronger projections to the subthalamic nucleus and parafascicular nucleus of the thalamus. These electrophysiological and anatomical differences suggest that Lhx6-GPe and PV-GPe neurons participate in different circuits with the potential to contribute to different aspects of motor function and dysfunction in disease.

The recovery from AP adaptation in sensorineural hearing loss

Conclusions: An abnormally slower action potential (AP) recovery from adaptation (decreased recovery, dR) was characteristically detected in many ears with sensorineural hearing loss (SNHL) but not Meniere's disease and idiopathic sudden SNHL. We assumed that this abnormal AP recovery from adaptation was attributed to an imbalance in the distributions of auditory neurons with high and low spontaneous firing rates. The significant difference of initial hearing level between dR and normal AP recovery groups (nR) was assumed to partially result from AP recovery being determined by the inner hair cell synapse, and not from outer hair cells. Objective: This study aimed to detect the AP recovery pattern in SNHL. Methods: Electrocochleography (ECochG) was performed transtympanically in 30 patients with SNHL. AP recovery was measured by a paired click stimulation paradigm as a function of inter-click intervals from 5 to 100 ms. Results: The high prevalence of dR (9 of 30 ears) appears to be a characteristic ECochG finding in SNHL. Initial hearing level differed significantly between dR and nR groups.

Lateral Hypothalamus Contains Two Types of Palatability-Related Taste Responses with Distinct Dynamics

The taste of foods, in particular the palatability of these tastes, exerts a powerful influence on our feeding choices. Although the lateral hypothalamus (LH) has long been known to regulate feeding behavior, taste processing in LH remains relatively understudied. Here, we examined single-unit LH responses in rats subjected to a battery of taste stimuli that differed in both chemical composition and palatability. Like neurons in cortex and amygdala, LH neurons produced a brief epoch of nonspecific responses followed by a protracted period of taste-specific firing. Unlike in cortex, however, where palatability-related information only appears 500 ms after the onset of taste-specific firing, taste specificity in LH was dominated by palatability-related firing, consistent with LH's role as a feeding center. Upon closer inspection, taste-specific LH neurons fell reliably into one of two subtypes: the first type showed a reliable affinity for palatable tastes, low spontaneous firing rates, phasic responses, and relatively narrow tuning; the second type showed strongest modulation to aversive tastes, high spontaneous firing rates, protracted responses, and broader tuning. Although neurons producing both types of responses were found within the same regions of LH, cross-correlation analyses suggest that they may participate in distinct functional networks. Our data shed light on the implementation of palatability processing both within LH and throughout the taste circuit, and may ultimately have implications for LH's role in the formation and maintenance of taste preferences and aversions.

Comparative study on song behavior, and ultra-structural, electrophysiological and immunoreactive properties in RA among deafened, untutored and normal-hearing Bengalese finches

To gain additional insight into how a birdsong is learned, we compared the songs of Bengalese finch males that were deafened early in development or raised without tutors to control finches that learned songs from adult models. Fewer note types and a more variable number of notes per bout were observed in untutored male songs, and no audible songs were detected in deafened males. We then investigated the ultrastructural, immunohistological, and electrophysiological correlates of the outcomes of song learning within the robust nucleus of the archopallium (RA), a forebrain nucleus for song production. In comparison to control birds, untutored and deafened birds had more synapses per unit volume, fewer vesicles per synapse, longer postsynaptic densities, and a lower proportion of perforated synapses, which suggest lower activity or decreased efficiency of synaptic transmission within the RA of the treated birds. For anesthetized birds, neurons within the RA of untutored and deafened males had lower spontaneous firing rates, fewer and shorter bursts, and higher coefficient of variation of the instantaneous firing rate than the normally reared males. Compared with controls, the untutored and deafened males had higher staining intensities within the RA of GABA and the GABAA receptor, less staining of tyrosine hydroxylase and no difference in the staining of NMDA receptors. Thus, both the ultrastructural and immunohistochemical results could explain for the stronger electrophysiological activities in normally reared birds. Because RA is involved in generating the motor commands, these data might account for the deficits in birds with abnormal song learning.

Baseline states and odour evoked responses of mitral and tufted cells in the awake mouse

Event Abstract Back to Event Baseline states and odour evoked responses of mitral and tufted cells in the awake mouse Mihaly Köllö1*, Anja Schmaltz1, Izumi Fukunaga1 and Andreas T. Schaefer1, 2 1 Max Planck Institute for Medical Research, Max Planck Research Group Behavioural Neurophysiology, Germany 2 Ruprecht-Karls-University, Faculty of Medicine, Germany Odour stimuli evoke activity patterns in the olfactory bulb, which are transformed in multiple steps by local microcircuits, before arriving to the cortex. Since inhibitory and excitatory synapses both exhibit short-term plasticity in this network, the baseline activities and properties of odour-evoked responses strongly determine, how much the individual neurons can influence information processing within the olfactory bulb. Therefore, gaining an unbiased picture about the states of different neurons of the network in the behaving animal is essential for understanding how inputs from different channels are transformed. We have performed blind whole-cell patch-clamp recordings in awake head-fixed mice to gain detailed and unbiased measurements of the spontaneous activity and odour-evoked responses of olfactory bulb neurons. Mitral and tufted cells show great diversity in their baseline resting membrane potentials and spike rates. Both in awake and anesthetized animals, a large proportion (>33%) of cells have very low spontaneous firing rates (<1 Hz). In awake animals, mitral and tufted cells exhibit both inhibitory and excitatory subthreshold and suprathreshold odour-evoked responses. Strong, phasic excitatory responses can be observed in a subset of cells, and these cells have hyperpolarized membrane potentials relative to other cells. Tufted cells exhibit strong excitatory responses more frequently than mitral cells. Granule cells are characterized by exceedingly hyperpolarized resting membrane potentials (-66.3±3.4 mV), and the virtually complete lack of spontaneous spikes. In response to specific odours they show prolonged subthreshold and only rarely suprathreshold excitatory responses. The observed large heterogeneity in base firing rates and odour-evoked responses suggests that different subpopulations of principal neurons, defined by their internal states, have distinct roles in local processing and points to the importance of intracellular recording techniques for studying olfactory networks. Keywords: in-vivo, Olfaction, patch-clamp Conference: Bernstein Conference 2012, Munich, Germany, 12 Sep - 14 Sep, 2012. Presentation Type: Poster Topic: Sensory processing and perception Citation: Köllö M, Schmaltz A, Fukunaga I and Schaefer AT (2012). Baseline states and odour evoked responses of mitral and tufted cells in the awake mouse. Front. Comput. Neurosci. Conference Abstract: Bernstein Conference 2012. doi: 10.3389/conf.fncom.2012.55.00254 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 10 May 2012; Published Online: 12 Sep 2012. * Correspondence: Dr. Mihaly Köllö, Max Planck Institute for Medical Research, Max Planck Research Group Behavioural Neurophysiology, Heidelberg, 69120, Germany, Mihaly.Kollo@mpimf-heidelberg.mpg.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Mihaly Köllö Anja Schmaltz Izumi Fukunaga Andreas T Schaefer Google Mihaly Köllö Anja Schmaltz Izumi Fukunaga Andreas T Schaefer Google Scholar Mihaly Köllö Anja Schmaltz Izumi Fukunaga Andreas T Schaefer PubMed Mihaly Köllö Anja Schmaltz Izumi Fukunaga Andreas T Schaefer Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Visual Representations by Cortical Somatostatin Inhibitory Neurons—Selective But with Weak and Delayed Responses

Somatostatin-expressing inhibitory (SOM) neurons in the sensory cortex consist mostly of Martinotti cells, which project ascending axons to layer 1. Due to their sparse distribution, the representational properties of these neurons remain largely unknown. By two-photon imaging guided cell-attached recordings, we characterized visual response and receptive field (RF) properties of SOM neurons and parvalbumin-expressing inhibitory (PV) neurons genetically labeled in the mouse primary visual cortex. In contrast to PV neurons, SOM neurons exhibit broader spikes, lower spontaneous firing rates, smaller On/Off subfields, and broader ranges of basic RF properties such as On/Off segregation, orientation and direction tunings. Notably, the level of orientation and direction selectivity is comparable to that of excitatory neurons, from weakly-tuned to highly selective, whereas PV neurons are in general unselective. Strikingly, the evoked spiking responses of SOM cells are ∼3- to 5-fold weaker and 20-25 ms delayed compared with those of PV neurons. The onset latency of the latter is consistent with that of inhibitory input to excitatory neurons. These functional differences between SOM and PV neurons exist in both layer 2/3 and 4. Our results suggest that SOM and PV neurons engage in cortical circuits in different manners: while PV neurons provide fast, strong but untuned feedforward inhibition to excitatory neurons, likely serving as a general gain control for the processing of ascending inputs, SOM neurons with their selective but delayed and weak inhibition may provide more specific gating of later arriving intracortical excitatory inputs on the distal dendrites.

Neural Heterogeneities and the coding of contrast envelopes

It is well known that higher order neurons respond to contrast envelopes (second order statistics) present in sensory stimuli. These contrast envelopes can be defined as the curve connecting successive peaks in the stimulus and can only be obtained through a nonlinear transformation of the stimulus such as the Hilbert transform. They contain important information that is decoded by the brain: for example, removal of these envelopes from speech severely reduces its intelligibility. While recent studies have shown potential mechanisms by which higher order neurons can acquire sensitivity to contrast envelopes, it is generally thought that peripheral sensory neurons do not respond to them. Using the electrosensory system of the weakly electric fish as a model we performed extracellular recordings from primary afferents while presenting contrast-modulated random amplitude modulations (AMs) of the fish’s quasi-sinusoidal electric field and found that about 45% of units responded to the time varying contrast envelope. Previous studies have shown that these afferents are spontaneously active and display large heterogeneities in their firing rates and burst firing properties: we therefore investigated whether these heterogeneities are linked to contrast envelope coding. We found that afferents with low spontaneous firing rate responded best to the contrast envelope due to higher levels of rectification. We next investigated the basis of this higher level of rectification using a simple phenomenological model of primary afferent activity. We found that varying levels of intrinsic noise as well as overall bias current in our model could reproduce our experimental results, suggesting that neural heterogeneities can significantly influence contrast envelope coding at the sensory periphery.

Singing-Related Neural Activity Distinguishes Four Classes of Putative Striatal Neurons in the Songbird Basal Ganglia

The striatum-the primary input nucleus of the basal ganglia-plays a major role in motor control and learning. Four main classes of striatal neuron are thought to be essential for normal striatal function: medium spiny neurons, fast-spiking interneurons, cholinergic tonically active neurons, and low-threshold spiking interneurons. However, the nature of the interaction of these neurons during behavior is poorly understood. The songbird area X is a specialized striato-pallidal basal ganglia nucleus that contains two pallidal cell types as well as the same four cell types found in the mammalian striatum. We recorded 185 single units in Area X of singing juvenile birds and, based on singing-related firing patterns and spike waveforms, find six distinct cell classes--two classes of putative pallidal neuron that exhibited a high spontaneous firing rate (> 60 Hz), and four cell classes that exhibited low spontaneous firing rates characteristic of striatal neurons. In this study, we examine in detail the four putative striatal cell classes. Type-1 neurons were the most frequently encountered and exhibited sparse temporally precise singing-related activity. Type-2 neurons were distinguished by their narrow spike waveforms and exhibited brief, high-frequency bursts during singing. Type-3 neurons were tonically active and did not burst, whereas type-4 neurons were inactive outside of singing and during singing generated long high-frequency bursts that could reach firing rates over 1 kHz. Based on comparison to the mammalian literature, we suggest that these four putative striatal cell classes correspond, respectively, to the medium spiny neurons, fast-spiking interneurons, tonically active neurons, and low-threshold spiking interneurons that are known to reside in area X.