Basal forebrain control of wakefulness and cortical rhythms.
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ABSTRACT:
SUBMITTER: Anaclet C
PROVIDER: S-EPMC4659943 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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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