Non-oscillatory measures of brain activity such as the spectral slope and Lempel-Ziv complexity are affected by many neurological disorders and modulated by sleep. A multitude of frequency ranges, particularly a broadband (encompassing the full spectrum) and narrowband approach, have been used especially for estimating the spectral slope. However, the effects of choosing different frequency ranges have not yet been explored in detail. Here, we evaluated the impact of sleep stage and task-engagement (resting, attention and memory) on slope and complexity in a narrow- (30 – 45Hz) and broadband (1 – 45Hz) frequency range in 28 healthy male human subjects (21.54 ± 1.90 years) using a within-subject design over two weeks with three recording nights and days per subject. We strived to determine how different brain states and frequency ranges affect slope and complexity and how the two measures perform in comparison. In the broadband range, the slope steepened, and complexity decreased continuously from wakefulne...

Self-ordered sequencing is an important executive function involving planning and executing a series of steps to achieve goal-directed outcomes. Lateral frontal cortex is implicated in this behavior, but downstream striatal outputs remain relatively unexplored. We trained marmosets on a three-stimulus self-ordered spatial sequencing task using a touch-sensitive screen to explore the role of caudate nucleus and putamen in random and fixed response arrays. By transiently blocking glutamatergic inputs to these regions, using intra-striatal CNQX microinfusions, we demonstrate that caudate and putamen are both required for, but contribute differently to, flexible and fixed sequencing. CNQX into either caudate or putamen impaired variable array accuracy, and infusions into both simultaneously elicited greater impairment. We demonstrated that continuous perseverative errors in variable array were caused by putamen infusions, likely due to interference with the putamen's established role in monitoring motor feedba...

Synchronization in the gamma band (25-150 Hz) is mediated by PV+ inhibitory interneurons, and evidence is accumulating for the essential role of gamma oscillations in cognition. Oscillations can arise in inhibitory networks via synaptic interactions between individual oscillatory neurons (mean-driven) or via strong recurrent inhibition that destabilizes the stationary background firing rate in the fluctuation-driven balanced state, causing an oscillation in the population firing rate. Previous theoretical work focused on model neurons with Hodgkin's type 1 excitability (integrators) connected by current-based synapses. Here we show that networks comprised of simple type 2 oscillators (resonators) exhibit a supercritical Hopf bifurcation between synchrony and asynchrony and a gradual transition via cycle skipping from coupled oscillators to stochastic population oscillator, as previously shown for type 1. We extended our analysis to homogeneous networks with conductance rather than current based synapses an...

Auditory perception can be significantly disrupted by noise. To discriminate sounds from noise, auditory scene analysis (ASA) extracts the functionally relevant sounds from acoustic input. The zebra finch communicates in noisy environments. Neurons in their secondary auditory pallial cortex (caudomedial nidopallium; NCM) can encode song from background chorus, or scenes, and this capacity may aid behavioral ASA. Furthermore, song processing is modulated by the rapid synthesis of neuroestrogens when hearing conspecific song. To examine whether neuroestrogens support neural and behavioral ASA in both sexes, we retrodialyzed fadrozole (aromatase inhibitor, FAD) and recorded in vivo awake extracellular NCM responses to songs and scenes. We found that FAD affected neural encoding of songs by decreasing responsiveness and timing reliability in inhibitory (narrow-spiking), but not in excitatory (broad-spiking) neurons. Congruently, FAD decreased neural encoding of songs in scenes for both cell types, particularly...

Layer 4 of the rodent somatosensory cortex has unitary structures called barrels that receive tactile information from individual vibrissae. Barrels in the anterolateral barrel subfield (ALBSF) are much smaller and have gained less attention than larger barrels in the posteromedial barrel subfield (PMBSF), though the former outnumber the latter. We compared the morphological features of barrels between the ALBSF and PMBSF in male mice using deformation-free tangential sections and confocal optical slice-based, precise reconstructions of barrels. The average volume of a single barrel in the ALBSF was 34.7% of that in the PMBSF, but the numerical density of parvalbumin (PV)-positive interneurons in the former was 1.49 times higher than that in the latter. Moreover, PV neuron density in septa was 2.08 times higher in the ALBSF than that in the PMBSF. The proportions of PV neuron number to both all neuron number and all GABAergic neuron number in the ALBSF were also higher than those in the PMBSF. Somata of PV...

The neural mechanisms underlying the exogenous coding and neural entrainment to repetitive auditory stimuli have seen a recent surge of interest. However, few studies have characterized how parametric changes in stimulus presentation alter entrained responses. We examined the degree to which the brain entrains to repeated speech (i.e., /ba/) and nonspeech (i.e., click) sounds using phase-locking value (PLV) analysis applied to multichannel human electroencephalogram (EEG) data. Passive cortico-acoustic tracking was investigated in N  = 24 normal young adults utilizing EEG source analyses that isolated neural activity stemming from both auditory temporal cortices. We parametrically manipulated the rate and periodicity of repetitive, continuous speech and click stimuli to investigate how speed and jitter in ongoing sound streams affect oscillatory entrainment. Neuronal synchronization to speech was enhanced at 4.5 Hz (the putative universal rate of speech) and showed a differential pattern to that of clicks,...

The preBötzinger complex (preBötC), located in the medulla, is the essential rhythm-generating neural network for breathing. The actions of opioids on this network impair its ability to generate robust, rhythmic output, contributing to life-threatening opioid-induced respiratory depression (OIRD). The occurrence of OIRD varies across individuals and internal and external states, increasing the risk of opioid use, yet the mechanisms of this variability are largely unknown. In this study, we utilize a computational model of the preBötC to perform several in silico experiments exploring how differences in network topology and the intrinsic properties of preBötC neurons influence the sensitivity of the network rhythm to opioids. We find that rhythms produced by preBötC networks in silico exhibit variable responses to simulated opioids, similar to the preBötC network in vitro. This variability is primarily due to random differences in network topology and can be manipulated by imposed changes in network connect...

The motor cortex comprises the primary descending circuits for flexible control of voluntary movements and is critically involved in motor skill learning. Motor skill learning is impaired in patients with Parkinson's disease, but the precise mechanisms of motor control and skill learning are still not well understood. Here we have used transgenic mice, electrophysiology, in situ hybridization, and neural tract-tracing methods to target genetically defined cell types expressing D1 and D2 dopamine receptors in the motor cortex. We observed that putative D1 and D2 dopamine receptor-expressing neurons (D1+ and D2+, respectively) are organized in highly segregated, nonoverlapping populations. Moreover, based on ex vivo patch-clamp recordings, we showed that D1+ and D2+ cells have distinct morphological and electrophysiological properties. Finally, we observed that chemogenetic inhibition of D2+, but not D1+, neurons disrupts skilled forelimb reaching in adult mice. Overall, these results demonstrate that dopami...

Problematic alcohol consumption is associated with deficits in decision-making and alterations in prefrontal cortex neural activity likely contribute. We hypothesized that the differences in cognitive control would be evident between male Wistars and a model of genetic risk: alcohol-preferring P rats. Cognitive control is split into proactive and reactive components. Proactive control maintains goal-directed behavior independent of a stimulus, whereas reactive control elicits goal-directed behavior at the time of a stimulus. We hypothesized that Wistars would show proactive control over alcohol seeking whereas P rats would show reactive control over alcohol seeking. Neural activity was recorded from the prefrontal cortex during an alcohol seeking task with two session types. On congruent sessions, the conditioned stimulus (CS+) was on the same side as alcohol access. Incongruent sessions presented alcohol opposite the CS+. Wistars, but not P rats, made more incorrect approaches during incongruent sessions,...

Dopamine neurons switch from tonic pacemaker activity to high-frequency bursts in response to salient stimuli. These bursts lead to superlinear increases in dopamine release, and the degree of this increase is highly dependent on firing frequency. The superlinearity and frequency dependence of dopamine release implicate short-term plasticity processes. The presynaptic Ca2+-sensor synaptotagmin-7 (SYT7) has suitable properties to mediate such short-term plasticity and has been implicated in regulating dopamine release from somatodendritic compartments. Here, we use a genetically encoded dopamine sensor and whole-cell electrophysiology in Syt7 KO mice to determine how SYT7 contributes to both axonal and somatodendritic dopamine release. We find that SYT7 mediates a hidden component of facilitation of release from dopamine terminals that can be unmasked by lowering initial release probability or by predepressing synapses with low-frequency stimulation. Depletion of SYT7 increased short-term depression and red...