Role of the Basal Forebrain Cholinergic Projection in Somatosensory Cortical Plasticity

Sachdev, Robert N. S., Shao-Ming Lu, Ron G. Wiley, and Ford F. Ebner. Role of the basal forebrain cholinergic projection in somatosensory cortical plasticity. J. Neurophysiol. 79: 3216–3228, 1998. Trimming all but two whiskers in adult rats produces a predictable change in cortical cell-evoked responses characterized by increased responsiveness to the two intact whiskers and decreased responsiveness to the trimmed whiskers. This type of synaptic plasticity in rat somatic sensory cortex, called “whisker pairing plasticity,” first appears in cells above and below the layer IV barrels. These are also the cortical layers that receive the densest cholinergic inputs from the nucleus basalis. The present study assesses whether the cholinergic inputs to cortex have a role in regulating whisker pairing plasticity. To do this, cholinergic basal forebrain fibers were eliminated using an immunotoxin specific for these fibers. A monoclonal antibody to the low-affinity nerve growth factor receptor 192 IgG, conjugated to the cytotoxin saporin, was injected into cortex to eliminate cholinergic fibers in the barrel field. The immunotoxin reduces acetylcholine esterase (AChE)-positive fibers in S1 cortex by >90% by 3 wk after injection. Sham-depleted animals in which either saporin alone or saporin unconjugated to 192 IgG is injected into the cortex produces no decrease in AChE-positive fibers in cortex. Sham-depleted animals show the expected plasticity in barrel column neurons. In contrast, no plasticity develops in the ACh-depleted, 7-day whisker-paired animals. These results support the conclusion that the basal forebrain cholinergic projection to cortex is an important facilitator of synaptic plasticity in mature cortex.

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Nucleus Basalis links sensory stimuli with delayed reinforcement to support learning

10.1101/663211 ◽

2019 ◽

Author(s):

W. Guo ◽

D.B. Polley

Keyword(s):

Basal Forebrain ◽

Neural Circuits ◽

Cortical Plasticity ◽

Cholinergic Neurons ◽

Nucleus Basalis ◽

Fear Learning ◽

Delayed Reinforcement ◽

Sensory Stimuli ◽

Sensory Inputs ◽

Cholinergic Basal Forebrain

SummaryLinking stimuli with delayed reinforcement requires neural circuits that can bridge extended temporal gaps. Auditory cortex (ACx) circuits reorganize to support auditory fear learning, but only when afferent sensory inputs temporally overlap with cholinergic reinforcement signals. Here we show that mouse ACx neurons rapidly reorganize to support learning, even when sensory and reinforcement cues are separated by a long gap. We found that cholinergic basal forebrain neurons bypass the temporal delay through multiplexed, short-latency encoding of sensory and reinforcement cues. At the initiation of learning, cholinergic neurons in Nucleus Basalis increase responses to conditioned sound frequencies and increase functional connectivity with ACx. By rapidly scaling up responses to sounds that predict reinforcement, cholinergic inputs jump the gap to align with bottom-up sensory traces and support associative cortical plasticity.

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Sleep is differently modulated by basal forebrain GABAA and GABAB receptors

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.281.1.r170 ◽

2001 ◽

Vol 281 (1) ◽

pp. R170-R175 ◽

Cited By ~ 21

Author(s):

Alfredo Manfridi ◽

Dario Brambilla ◽

Mauro Mancia

Keyword(s):

Basal Forebrain ◽

Slow Wave Sleep ◽

Gabab Receptors ◽

Nucleus Basalis ◽

Receptor Subtype ◽

Sleep Regulation ◽

Sleep Parameters ◽

Polygraphic Recordings ◽

Sleep Modulation

There is evidence that GABA plays a major role in sleep regulation. GABAA receptor agonists and different compounds interacting with the GABAA receptor complex, such as barbiturates and benzodiazepines, can interfere with the sleep/wake cycle. On the other hand, there is very little information about the possible role of GABAB receptors in sleep modulation. The nucleus basalis of Meynert (NBM), a cholinergic area in the basal forebrain, plays a pivotal role in the modulation of sleep and wakefulness, and both GABAA and GABABreceptors have been described within the NBM. This study used unilateral infusions in the NBM to determine the effects of 3-hydroxy-5-aminomethylisoxazole hydrobromide (muscimol hydrobromide, a GABAA receptor subtype agonist) and β-(aminomethyl)-4-chlorobenzenepropanoic acid (baclofen, a GABAB receptor subtype agonist) on sleep parameters in freely moving rats by means of polygraphic recordings. Muscimol (0.5 nmol) and baclofen (0.7 nmol) induced an increase in slow-wave sleep and an inhibition of wakefulness. Muscimol, but not baclofen, also caused a decrease in desynchronized sleep parameters. The results reported here indicate that 1) the NBM activation of both GABAA and GABAB receptors influences the sleep/wake cycle, and 2) GABAA but not GABAB receptors are important for desynchronized sleep modulation, suggesting that the two GABAergic receptors play different roles in sleep modulation.

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Role of p75 neurotrophin receptor in normal cholinergic basal forebrain function in adults

10.14264/uql.2016.230 ◽

2016 ◽

Author(s):

Zoran Boskovic

Keyword(s):

Basal Forebrain ◽

Neurotrophin Receptor ◽

P75 Neurotrophin Receptor ◽

Cholinergic Basal Forebrain

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Augmentation of Plasticity of the Central Auditory System by the Basal Forebrain and/or Somatosensory Cortex

Journal of Neurophysiology ◽

10.1152/jn.00968.2001 ◽

2003 ◽

Vol 89 (1) ◽

pp. 90-103 ◽

Cited By ~ 71

Author(s):

Xiaofeng Ma ◽

Nobuo Suga

Keyword(s):

Somatosensory Cortex ◽

Auditory System ◽

Basal Forebrain ◽

Cortical Neurons ◽

Electric Stimulation ◽

Cortical Plasticity ◽

Frequency Tuning ◽

Cortical Stimulation ◽

Cholinergic Basal Forebrain ◽

Stimulation Of

Auditory conditioning (associative learning) or focal electric stimulation of the primary auditory cortex (AC) evokes reorganization (plasticity) of the cochleotopic (frequency) map of the inferior colliculus (IC) as well as that of the AC. The reorganization results from shifts in the best frequencies (BFs) and frequency-tuning curves of single neurons. Since the importance of the cholinergic basal forebrain for cortical plasticity and the importance of the somatosensory cortex and the corticofugal auditory system for collicular and cortical plasticity have been demonstrated, Gao and Suga proposed a hypothesis that states that the AC and corticofugal system play an important role in evoking auditory collicular and cortical plasticity and that auditory and somatosensory signals from the cerebral cortex to the basal forebrain play an important role in augmenting collicular and cortical plasticity. To test their hypothesis, we studied whether the amount and the duration of plasticity of both collicular and cortical neurons evoked by electric stimulation of the AC or by acoustic stimulation were increased by electric stimulation of the basal forebrain and/or the somatosensory cortex. In adult big brown bats ( Eptesicus fuscus), we made the following major findings. 1) Collicular and cortical plasticity evoked by electric stimulation of the AC is augmented by electric stimulation of the basal forebrain. The amount of augmentation is larger for cortical plasticity than for collicular plasticity. 2) Collicular and cortical plasticity evoked by AC stimulation is augmented by somatosensory cortical stimulation mimicking fear conditioning. The amount of augmentation is larger for cortical plasticity than for collicular plasticity. 3) Collicular and cortical plasticity evoked by both AC and basal forebrain stimulations is further augmented by somatosensory cortical stimulation. 4) A lesion of the basal forebrain tends to reduce collicular and cortical plasticity evoked by AC stimulation. The reduction is small and statistically insignificant for collicular plasticity but significant for cortical plasticity. 5) The lesion of the basal forebrain eliminates the augmentation of collicular and cortical plasticity that otherwise would be evoked by somatosensory cortical stimulation. 6) Collicular and cortical plasticity evoked by repetitive acoustic stimuli is augmented by basal forebrain and/or somatosensory cortical stimulation. However, the lesion of the basal forebrain eliminates the augmentation of collicular and cortical plasticity that otherwise would be evoked by somatosensory cortical stimulation. These findings support the hypothesis proposed by Gao and Suga.

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Basal forebrain cholinergic neurons are part of the threat memory engram

10.1101/2021.05.02.442364 ◽

2021 ◽

Author(s):

Prithviraj Rajebhosale ◽

Mala R Ananth ◽

Richard B Crouse ◽

Li Jiang ◽

Gretchen López- Hernández ◽

...

Keyword(s):

Basal Forebrain ◽

Basolateral Amygdala ◽

Cholinergic Neurons ◽

Nucleus Basalis ◽

Early Gene ◽

Intrinsic Excitability ◽

Cholinergic Basal Forebrain ◽

Basal Forebrain Cholinergic Neurons ◽

Cholinergic Signaling ◽

Memory Engram

Although the engagement of cholinergic signaling in threat memory is well established (Knox, 2016a), our finding that specific cholinergic neurons are requisite partners in a threat memory engram is likely to surprise many. Neurons of the basal forebrain nucleus basalis and substantia innonimata (NBM/SIp) comprise the major source of cholinergic input to the basolateral amygdala (BLA), whose activation are required for both the acquisition and retrieval of cued threat memory and innate threat response behavior. The retrieval of threat memory by the presentation of the conditioning tone alone elicits acetylcholine (ACh) release in the BLA and the BLA-projecting cholinergic neurons manifest immediate early gene responses and display increased intrinsic excitability for 2-5 hours following the cue-elicited memory response to the conditioned stimulus. Silencing cue-associated engram-enrolled cholinergic neurons prevents the expression of the defensive response and the subset of cholinergic neurons activated by cue is distinct from those engaged by innate threat. Taken together we find that distinct populations of cholinergic neurons are recruited to signal distinct aversive stimuli via the BLA, demonstrating exquisite, functionally refined organization of specific types of memory within the cholinergic basal forebrain.

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