Cholinergic Neurons Excite Cortically Projecting Basal Forebrain GABAergic Neurons

Yang, Chun; Mckenna, James T; Zant, Janneke C.; Winston, Stuart; Basheer, Radhika; Brown, Ritchie E.

doi:10.1523/jneurosci.3235-13.2014

Cited by 82 publications

(87 citation statements)

References 43 publications

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“…Atrophy of BF cholinergic neurons has been widely replicated both in this disease and in normal aging (48). Cholinergic neurons normally excite BF GABA/PV neurons (41), and loss of BF GABA/PV neurons has been noted in aged mice which have accumulation of extracellular amyloid plaques and episodic-like memory impairments (49). Thus, reduced activity caused by the loss of cholinergic neurons or the direct loss of BF GABA/PV neurons may be partially responsible for cortical oscillation abnormalities and associated cognitive impairments in aging and Alzheimer's disease.…”

Section: Discussionmentioning

confidence: 97%

“…Here, we found that saporin lesions of BF cholinergic neurons, resulting in a 70% loss of this cell type, did not significantly affect the ability of BF PV stimulation to induce a cortical 40-Hz response, suggesting that cholinergic neurons are not required. However, under normal conditions, cholinergic and GABA/PV neurons likely work together to control cortical activation and GBO activity because cholinergic neurons strongly excite identified BF GABA and PV neurons in vitro (41).…”

Section: Discussionmentioning

confidence: 99%

“…Cortical EEG recordings, immunohistochemistry, and in vitro recordings were performed as described previously (21,41,44). Details of the experimental procedures are provided in SI Materials and Methods.…”

Section: Discussionmentioning

confidence: 99%

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Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations

Kim

Thankachan

Mckenna

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

266

256

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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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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations

Kim

Thankachan

Mckenna

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

266

256

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“…Thus both anatomical and functional substrates by which BF gamma oscillations could influence DMN cortical areas have been documented. However, parvalbumin GABAergic cells are depolarized by cholinergic activation (65), so that independent regulation of cholinergic and GABAergic projection networks requires additional mechanisms. It is thus possible that GABAergic and glutamatergic BF neurons cooperate to mediate the influence of the BF on the DMN.…”

Section: Discussionmentioning

confidence: 99%

Basal forebrain contributes to default mode network regulation

Nair

Klaassen

Arató³

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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The default mode network (DMN) is a collection of cortical brain regions that is active during states of rest or quiet wakefulness in humans and other mammalian species. A pertinent characteristic of the DMN is a suppression of local field potential gamma activity during cognitive task performance as well as during engagement with external sensory stimuli. Conversely, gamma activity is elevated in the DMN during rest. Here, we document that the rat basal forebrain (BF) exhibits the same pattern of responses, namely pronounced gamma oscillations during quiet wakefulness in the home cage and suppression of this activity during active exploration of an unfamiliar environment. We show that gamma oscillations are localized to the BF and that gamma-band activity in the BF has a directional influence on a hub of the rat DMN, the anterior cingulate cortex, during DMNdominated brain states. The BF is well known as an ascending, activating, neuromodulatory system involved in wake-sleep regulation, memory formation, and regulation of sensory information processing. Our findings suggest a hitherto undocumented role of the BF as a subcortical node of the DMN, which we speculate may be important for switching between internally and externally directed brain states. We discuss potential BF projection circuits that could underlie its role in DMN regulation and highlight that certain BF nuclei may provide potential target regions for up-or down-regulation of DMN activity that might prove useful for treatment of DMN dysfunction in conditions such as epilepsy or major depressive disorder.gamma suppression | anterior cingulate cortex | granger causality A highly consistent finding across a wide range of functional imaging studies in humans is that a network of brain regions, referred to as the "default mode network" (DMN), increases its activity during passive mental states compared with the performance of cognitive tasks. This was initially shown in a metaanalysis of several PET studies (1), in which a distribution of brain regions broadly including the medial prefrontal, retrosplenial, and anterior cingulate cortex (ACC), as well as lateral parietal and temporal cortices, was shown to be activated when subjects were in a state of quiet restfulness. The DMN areas are thought to form a cohesive set of intrinsically coupled brain regions, such that fMRI activations in its component regions exhibit similar time courses, allowing them to be identified reliably using seed-region analysis (2-4). Activity in the DMN exhibits anticorrelation with a complementary, largely nonoverlapping, set of fronto-parietal brain areas known as the "dorsal attention network" (DAN) (5). It should be noted, however, that particular brain structures may harbor functionally heterogeneous elements and thus may contribute to multiple functions, as was shown for the ACC (6). During wakefulness, the human brain thus alternates between DAN-and DMN-dominated activation states, corresponding to effortful cognitive task performance on the one hand and quiet restful...

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“…Such studies have almost exclusively focused on recording the activity of single neurons, often labelled according to cell type, and linking their firing patterns to the cortical EEG (Duque et al, 2000;Manns et al, 2000aManns et al, , 2000bHassani et al, 2009), wake/sleep regulation (Szymusiak et al, 2000;Lee et al, 2004Lee et al, , 2005, aspects of sensory stimulation (Lin and Nicolelis, 2008;Nguyen and Lin, 2014), and behavioral task performance (Thomson et al, 2014;Tingley et al, 2014Tingley et al, , 2015. Convergent evidence (Zaborszky et al, 1999;Yang et al, 2014;Xu et al, 2015) indicates that BF contains multiple interconnected and heterogeneous networks, which operate as an ensemble to modulate cortical state and play distinct roles during sleep and wakefulness. It is thus quite surprising that very little is known about BF ensemble activity, as estimated by the LFP; but see (Quinn et al, 2010;Whitmore and Lin, 2016).…”

Section: Introductionmentioning

confidence: 99%

Gamma band directional interactions between basal forebrain and visual cortex during wake and sleep states

Nair

Klaassen

Poirot

et al. 2016

Journal of Physiology-Paris

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The basal forebrain (BF) is an important regulator of cortical excitability and responsivity to sensory stimuli, and plays a major role in wake-sleep regulation. While the impact of BF on cortical EEG or LFP signals has been extensively documented, surprisingly little is known about LFP activity within BF. Based on bilateral recordings from rats in their home cage, we describe endogenous LFP oscillations in the BF during quiet wakefulness, rapid eye movement (REM) and slow wave sleep (SWS) states. Using coherence and Granger causality methods, we characterize directional influences between BF and visual cortex (VC) during each of these states. We observed pronounced BF gamma activity particularly during wakefulness, as well as to a lesser extent during SWS and REM. During wakefulness, this BF gamma activity exerted a directional influence on VC that was associated with cortical excitation. During SWS but not REM, there was also a robust directional gamma band influence of BF on VC. In all three states, directional influence in the gamma band was only present in BF to VC direction and tended to be regulated specifically within each brain hemisphere. Locality of gamma band LFPs to the BF was confirmed by demonstration of phase locking of local spiking activity to the gamma cycle. We report novel aspects of endogenous BF LFP oscillations and their relationship to cortical LFP signals during sleep and wakefulness. We link our findings to known aspects of GABAergic BF networks that likely underlie gamma band LFP activations, and show that the Granger causality analyses can faithfully recapitulate many known attributes of these networks.

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Cholinergic Neurons Excite Cortically Projecting Basal Forebrain GABAergic Neurons

Cited by 82 publications

References 43 publications

Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations

Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations

Basal forebrain contributes to default mode network regulation

Gamma band directional interactions between basal forebrain and visual cortex during wake and sleep states

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