Optogenetic stimulation of basal forebrain parvalbumin neurons modulates the cortical topography of auditory steady-state responses.
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ABSTRACT:
SUBMITTER: Hwang E
PROVIDER: S-EPMC6532347 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:We present high-density EEG datasets of auditory steady-state responses (ASSRs) recorded from the cortex of freely moving mice with or without optogenetic stimulation of basal forebrain parvalbumin (BF-PV) neurons, known as a subcortical hub circuit for the global workspace. The dataset of ASSRs without BF-PV stimulation (dataset 1) contains raw 36-channel EEG epochs of ASSRs elicited by 10, 20, 30, 40, and 50 Hz click trains and time stamps of stimulations. The dataset of ASSRs with BF-PV stimulation (dataset 2) contains raw 36-channel EEG epochs of 40-Hz ASSRs during BF-PV stimulation with latencies of 0, 6.25, 12.5, and 18.75 ms and time stamps of stimulations. We provide the datasets and step-by-step tutorial analysis scripts written in Python, allowing for descriptions of the event-related potentials, spectrograms, and the topography of power. We complement this experimental dataset with simulation results using a time-dependent perturbation on coupled oscillators. This publicly available dataset will be beneficial to the experimental and computational neuroscientists.
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Project description:Neuronal activity can modify Alzheimer's disease pathology. Overexcitation of neurons can facilitate disease progression whereas the induction of cortical gamma oscillations can reduce amyloid load and improve cognitive functions in mouse models. Although previous studies have induced cortical gamma oscillations by either optogenetic activation of cortical parvalbumin-positive (PV+) neurons or sensory stimuli, it is still unclear whether other approaches to induce gamma oscillations can also be beneficial. Here we show that optogenetic activation of PV+ neurons in the basal forebrain (BF) increases amyloid burden, rather than reducing it. We applied 40 Hz optical stimulation in the BF by expressing channelrhodopsin-2 (ChR2) in PV+ neurons of 5xFAD mice. After 1-h induction of cortical gamma oscillations over three days, we observed the increase in the concentration of amyloid-β42 in the frontal cortical region, but not amyloid-β40. Amyloid plaques were accumulated more in the medial prefrontal cortex and the septal nuclei, both of which are targets of BF PV+ neurons. These results suggest that beneficial effects of cortical gamma oscillations on Alzheimer's disease pathology can depend on the induction mechanisms of cortical gamma oscillations.
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Project description:Acetylcholine (ACh) release in the cortex is critical for learning, memory, attention, and plasticity. Here, we explore the cholinergic and noncholinergic projections from the basal forebrain (BF) to the auditory cortex using classical retrograde and monosynaptic viral tracers deposited in electrophysiologically identified regions of the auditory cortex. Cholinergic input to both primary (A1) and nonprimary auditory cortical (belt) areas originates in a restricted area in the caudal BF within the globus pallidus (GP) and in the dorsal part of the substantia innominata (SId). On the other hand, we found significant differences in the proportions of cholinergic and noncholinergic projection neurons to primary and nonprimary auditory areas. Inputs to A1 projecting cholinergic neurons were restricted to the GP, caudate-putamen, and the medial part of the medial geniculate body, including the posterior intralaminar thalamic group. In addition to these areas, afferents to belt-projecting cholinergic neurons originated from broader areas, including the ventral secondary auditory cortex, insular cortex, secondary somatosensory cortex, and the central amygdaloid nucleus. These findings support a specific BF projection pattern to auditory cortical areas. Additionally, these findings point to potential functional differences in how ACh release may be regulated in the A1 and auditory belt areas.
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Project description:Cortical gamma band oscillations (GBO, 30-80 Hz, typically ∼40 Hz) are involved in higher cognitive functions such as feature binding, attention, and working memory. GBO abnormalities are a feature of several neuropsychiatric disorders associated with dysfunction of cortical fast-spiking interneurons containing the calcium-binding protein parvalbumin (PV). GBO vary according to the state of arousal, are modulated by attention, and are correlated with conscious awareness. However, the subcortical cell types underlying the state-dependent control of GBO are not well understood. Here we tested the role of one cell type in the wakefulness-promoting basal forebrain (BF) region, cortically projecting GABAergic neurons containing PV, whose virally transduced fibers we found apposed cortical PV interneurons involved in generating GBO. Optogenetic stimulation of BF PV neurons in mice preferentially increased cortical GBO power by entraining a cortical oscillator with a resonant frequency of ∼40 Hz, as revealed by analysis of both rhythmic and nonrhythmic BF PV stimulation. Selective saporin lesions of BF cholinergic neurons did not alter the enhancement of cortical GBO power induced by BF PV stimulation. Importantly, bilateral optogenetic inhibition of BF PV neurons decreased the power of the 40-Hz auditory steady-state response, a read-out of the ability of the cortex to generate GBO used in clinical studies. Our results are surprising and novel in indicating that this presumptively inhibitory BF PV input controls cortical GBO, likely by synchronizing the activity of cortical PV interneurons. BF PV neurons may represent a previously unidentified therapeutic target to treat disorders involving abnormal GBO, such as schizophrenia.
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Project description:The ability to rapidly arouse from sleep is important for survival. However, increased arousals in patients with sleep apnea and other disorders prevent restful sleep and contribute to cognitive, metabolic, and physiologic dysfunction [1, 2]. Little is currently known about which neural systems mediate these brief arousals, hindering the development of treatments that restore normal sleep. The basal forebrain (BF) receives inputs from many nuclei of the ascending arousal system, including the brainstem parabrachial neurons, which promote arousal in response to elevated blood carbon dioxide levels, as seen in sleep apnea [3]. Optical inhibition of the terminals of parabrachial neurons in the BF impairs cortical arousals to hypercarbia [4], but which BF cell types mediate cortical arousals in response to hypercarbia or other sensory stimuli is unknown. Here, we tested the role of BF parvalbumin (PV) neurons in arousal using optogenetic techniques in mice. Optical stimulation of BF-PV neurons produced rapid transitions to wakefulness from non-rapid eye movement (NREM) sleep but did not affect REM-wakefulness transitions. Unlike previous studies of BF glutamatergic and cholinergic neurons, arousals induced by stimulation of BF-PV neurons were brief and only slightly increased total wake time, reminiscent of clinical findings in sleep apnea [5, 6]. Bilateral optical inhibition of BF-PV neurons increased the latency to arousal produced by exposure to hypercarbia or auditory stimuli. Thus, BF-PV neurons are an important component of the brain circuitry that generates brief arousals from sleep in response to stimuli, which may indicate physiological dysfunction or danger to the organism.
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Project description:Auditory prostheses can partially restore speech comprehension when hearing fails. Sound coding with current prostheses is based on electrical stimulation of auditory neurons and has limited frequency resolution due to broad current spread within the cochlea. In contrast, optical stimulation can be spatially confined, which may improve frequency resolution. Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). Optogenetic stimulation of spiral ganglion neurons (SGNs) activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses. Furthermore, optogenetic stimulation of SGNs restored auditory activity in deaf mice. Approximation of the spatial spread of cochlear excitation by recording local field potentials (LFPs) in the inferior colliculus in response to suprathreshold optical, acoustic, and electrical stimuli indicated that optogenetic stimulation achieves better frequency resolution than monopolar electrical stimulation. Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. Our study demonstrates a strategy for optogenetic stimulation of the auditory pathway in rodents and lays the groundwork for future applications of cochlear optogenetics in auditory research and prosthetics.
| S-EPMC3934189 | biostudies-literature
Project description:Across species, the performance of vocal signals can be modulated by the social environment. Zebra finches, for example, adjust their song performance when singing to females ('female-directed' or FD song) compared to when singing in isolation ('undirected' or UD song). These changes are salient, as females prefer the FD song over the UD song. Despite the importance of these performance changes, the neural mechanisms underlying this social modulation remain poorly understood. Previous work in finches has established that expression of the immediate early gene EGR1 is increased during singing and modulated by social context within the vocal control circuitry. Here, we examined whether particular neural subpopulations within those vocal control regions exhibit similar modulations of EGR1 expression. We compared EGR1 expression in neurons expressing parvalbumin (PV), a calcium buffer that modulates network plasticity and homeostasis, among males that performed FD song, males that produced UD song, or males that did not sing. We found that, overall, singing but not social context significantly affected EGR1 expression in PV neurons throughout the vocal control nuclei. We observed differences in EGR1 expression between two classes of PV interneurons in the basal ganglia nucleus Area X. Additionally, we found that singing altered the amount of PV expression in neurons in HVC and Area X and that distinct PV interneuron types in Area X exhibited different patterns of modulation by singing. These data indicate that throughout the vocal control circuitry the singing-related regulation of EGR1 expression in PV neurons may be less influenced by social context than in other neuron types and raise the possibility of cell-type specific differences in plasticity and calcium buffering.
| S-EPMC5325550 | biostudies-literature
Project description:Wakefulness, along with fast cortical rhythms and associated cognition, depend on the basal forebrain (BF). BF cholinergic cell loss in dementia and the sedative effect of anti-cholinergic drugs have long implicated these neurons as important for cognition and wakefulness. The BF also contains intermingled inhibitory GABAergic and excitatory glutamatergic cell groups whose exact neurobiological roles are unclear. Here we show that genetically targeted chemogenetic activation of BF cholinergic or glutamatergic neurons in behaving mice produced significant effects on state consolidation and/or the electroencephalogram but had no effect on total wake. Similar activation of BF GABAergic neurons produced sustained wakefulness and high-frequency cortical rhythms, whereas chemogenetic inhibition increased sleep. Our findings reveal a major contribution of BF GABAergic neurons to wakefulness and the fast cortical rhythms associated with cognition. These findings may be clinically applicable to manipulations aimed at increasing forebrain activation in dementia and the minimally conscious state.
| S-EPMC4659943 | biostudies-literature
Project description:The cholinergic neurons of the basal forebrain (BF) provide virtually all of the brain's cortical and amygdalar cholinergic input. They are particularly vulnerable to neuropathology in early Alzheimer's disease (AD) and may trigger the emergence of neuropathology in their cortico-amygdalar projection system through cholinergic denervation and trans-synaptic spreading of misfolded proteins. We examined whether longitudinal degeneration within the BF can explain longitudinal cortico-amygdalar degeneration in older human adults with abnormal cerebrospinal fluid biomarkers of AD neuropathology. We focused on two BF subregions, which are known to innervate cortico-amygdalar regions via two distinct macroscopic cholinergic projections. To further assess whether structural degeneration of these regions in AD reflects cholinergic denervation, we used the [18F] FEOBV radiotracer, which binds to cortico-amygdalar cholinergic terminals. We found that the two BF subregions explain spatially distinct patterns of cortico-amygdalar degeneration, which closely reflect their cholinergic projections, and overlap with [18F] FEOBV indices of cholinergic denervation.
| S-EPMC8840819 | biostudies-literature
Project description:AimsThe basal forebrain (BF) plays an essential role in wakefulness and cognition. Two subtypes of BF gamma-aminobutyric acid (GABA) neurons, including somatostatin-expressing (GABASOM ) and parvalbumin-positive (GABAParv ) neurons, function differently in mediating the natural sleep-wake cycle. Since the loss of consciousness induced by general anesthesia and the natural sleep-wake cycle probably share similar mechanisms, it is important to clarify the accurate roles of these neurons in general anesthesia procedure.MethodsBased on two transgenic mouse lines expressing SOM-IRES-Cre and PV-IRES-Cre, we used a combination of genetic activation, inactivation, and chronic ablation approaches to further explore the behavioral and electroencephalography (EEG) roles of BFSOM and BFParv neurons in general anesthesia. After a single intravenous injection of propofol and the induction and recovery times of isoflurane anesthesia, the anesthesia time was compared. The changes in cortical EEG under different conditions were also compared.ResultsActivation of BF GABASOM neurons facilitates both the propofol and isoflurane anesthesia, manifesting as a longer anesthesia duration time with propofol anesthesia and a fast induction time and longer recovery time with isoflurane anesthesia. Moreover, BF GABASOM -activated mice displayed a greater suppression of cortical electrical activity during anesthesia, showing an increase in δ power bands or a simultaneous decrease in high-frequency power bands. However, only a limited and nuanced effect on propofol and isoflurane anesthesia was observed with the manipulated BF GABAParv neurons.ConclusionsOur results suggested that BF GABASOM neurons play a critical role in propofol and isoflurane general anesthesia, while BF GABAParv neurons appeared to have little effect.
| S-EPMC8193699 | biostudies-literature