A role for acetylcholine in conditioning-related responses of rat frontal cortex neurons: microiontophoretic evidence

Pirch, James H.; Turco, Kathy; Rucker, Hubert K.

doi:10.1016/0006-8993(92)91366-m

Cited by 74 publications

(20 citation statements)

References 37 publications

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“…The correlation between participation in conditioning and sensitivity to acetylcholine was statistically signi®cant. In another series of experiments, conditional changes in cortical cells depended on acetylcholine in approximately 90% of cells recorded (Rigdon and Pirch, 1986;Pirch et al, 1992). This is quite a remarkable correspondence considering that only 14±16% of cortical cells appear to be cholinoceptive.…”

Section: Introductionmentioning

confidence: 72%

A structural basis for memory storage in mammals

Woolf

1998

Progress in Neurobiology

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AbstractÐIt is proposed that altered dendrite length and de novo formation of new dendrite branches in cholinoceptive cells are responsible for long-term memory storage, a process enabled by the degradation of microtubule-associated protein-2. These memories are encoded as modality-speci®c associable representations. Accordingly, associable representations are con®ned to cytoarchitectonic modules of the cerebral cortex, hippocampus, and amygdala. The proposed sequence of events leading to long-term storage in cholinoceptive dendrites begins with changes in neuronal activity, then in neurotrophin release, followed by enhanced acetylcholine release, muscarinic response, calcium in¯ux, degradation of microtubule-associated protein-2, and ®nally new dendrite structure. Hypothetically, each associable representation consists of altered dendrite segments from approximately 5000±15 000 cholinoceptive cells contained within one or a few module(s). Simultaneous restructuring during consolidation of long-term memory is hypothesized to result in a similar infrastructure among dendrite sets, facilitating co-activation of those dendrite sets by neurotransmitters such as acetylcholine, and conceivably enabling high energy interactions between those dendrites by phenomena such as quantum optical coherence. Based on the speci®c architecture proposed, it is estimated that the human telencephalon contains enough dendrites to encode 50 million associable representations in a lifetime, or put another way, to encode one new associable representation each minute. The implications that this proposal has regarding treatments for Alzheimer's disease are also discussed. #

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Section: Introductionmentioning

confidence: 72%

A structural basis for memory storage in mammals

Woolf

1998

Progress in Neurobiology

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“…*p Ͻ 0.05 or **p Ͻ 0.001. ms interval used in our PPI studies (Hu et al, 2007). Determining with certainty the level of M-channel activation in vivo during the first acoustic stimulus would require analysis of firing changes with in vivo electrophysiology, which is beyond the scope of the present work, although other studies have indicated that mPFC neurons often show strong increases in firing to potent or novel stimuli (Pirch et al, 1992;Baeg et al, 2001;Jackson and Moghaddam, 2006). Interestingly, we did not observe enhanced acoustic startle reactivity in Kcnq2(tm1Dgen)/ϩ mice in the absence of prepulses, suggesting that M-channel-induced changes in neuronal excitability specifically after the prepulse stimulus may be critical for modulating the subsequent response to the startle stimulus.…”

Section: Discussionmentioning

confidence: 96%

Protein Phosphatase 2A and Glycogen Synthase Kinase 3 Signaling Modulate Prepulse Inhibition of the Acoustic Startle Response by Altering Cortical M-Type Potassium Channel Activity

Kaufholdt¹,

Berger²,

Hopf³

et al. 2010

Journal of Neuroscience

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There is considerable interest in the regulation of sensorimotor gating, since deficits in this process could play a critical role in the symptoms of schizophrenia and other psychiatric disorders. Sensorimotor gating is often studied in humans and rodents using the prepulse inhibition of the acoustic startle response (PPI) model, in which an acoustic prepulse suppresses behavioral output to a startle-inducing stimulus. However, the molecular and neural mechanisms underlying PPI are poorly understood. Here, we show that a regulatory pathway involving protein phosphatase 2A (PP2A), glycogen synthase kinase 3 ␤ (GSK3␤), and their downstream target, the M-type potassium channel, regulates PPI. Mice (Mus musculus) carrying a hypomorphic allele of Ppp2r5␦, encoding a regulatory subunit of PP2A, show attenuated PPI. This PPP2R5␦ reduction increases the phosphorylation of GSK3␤ at serine 9, which inactivates GSK3␤, indicating that PPP2R5␦ positively regulates GSK3␤ activity in the brain. Consistently, genetic and pharmacological manipulations that reduce GSK3␤ function attenuate PPI. The M-type potassium channel subunit, KCNQ2, is a putative GSK3␤ substrate. Genetic reduction of Kcnq2 also reduces PPI, as does systemic inhibition of M-channels with linopirdine. Importantly, both the GSK3 inhibitor 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)1H-pyrrole-2,5-dione (SB216763) and linopirdine reduce PPI when directly infused into the medial prefrontal cortex (mPFC). Whole-cell electrophysiological recordings of mPFC neurons show that SB216763 and linopirdine have similar effects on firing, and GSK3 inhibition occludes the effects of M-channel inhibition. These data support a previously uncharacterized mechanism by which PP2A/GSK3␤ signaling regulates M-type potassium channel activity in the mPFC to modulate sensorimotor gating.

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“…In rat frontal cortex, ACh released by basal forebrain afferents has been implicated in the generation (Rigdon and Pirch, 1986) and modulation (Pirch et al, 1992) of conditioned neuronal responses. In cat parietal and occipital cortex, facilitatory effects of iontophoresed ACh on somatosensory and visual responses have been documented to be predominant (Sillito and Kemp, 1983;Tremblay et al, 1990).…”

Section: Areal and Laminar Distribution Of The Ach Innervationmentioning

confidence: 99%

Cholinergic innervation in adult rat cerebral cortex: A quantitative immunocytochemical description

2000

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A method for determining the length of acetylcholine (ACh) axons and number of ACh axon varicosities (terminals) in brain sections immunostained for choline acetyltransferase (ChAT) was used to estimate the areal and laminar densities of this innervation in the frontal (motor), parietal (somatosensory), and occipital (visual) cortex of adult rat. The number of ACh varicosities per length of axon (4 per 10 microm) appeared constant in the different layers and areas. The mean density of ACh axons was the highest in the frontal cortex (13.0 m/mm(3) vs. 9.9 and 11.0 m/mm(3) in the somatosensory and visual cortex, respectively), as was the mean density of ACh varicosities (5.4 x 10(6)/mm(3) vs. 3.8 and 4.6 x 10(6)/mm(3)). In all three areas, layer I displayed the highest laminar densities of ACh axons and varicosities (e.g., 13.5 m/mm(3) and 5.4 x 10(6)/mm(3) in frontal cortex). The lowest were those of layer IV in the parietal cortex (7.3 m/mm(3) and 2.9 x 10(6)/mm(3)). The lengths of ACh axons under a 1 mm(2) surface of cortex were 26.7, 19.7, and 15.3 m in the frontal, parietal, and occipital areas, respectively, for corresponding numbers of 11.1, 7.7, and 6.4 x 10(6) ACh varicosities. In the parietal cortex, this meant a total of 1.2 x 10(6) synaptic ACh varicosities under a 1 mm(2) surface, 48% of which in layer V alone, according to previous electron microscopic estimates of synaptic incidence. In keeping with the notion that the synaptic component of ACh transmission in cerebral cortex is preponderant in layer V, these quantitative data suggest a role for this innervation in the processing of cortical output as well as input. Extrapolation of particular features of this system in terms of total axon length and number of varicosities in whole cortex, length of axons and number of varicosities per cortically projecting neuron, and concentration of ACh per axon varicosity, should also help in arriving at a better definition of its roles and functional properties in cerebral cortex.

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A role for acetylcholine in conditioning-related responses of rat frontal cortex neurons: microiontophoretic evidence

Cited by 74 publications

References 37 publications

A structural basis for memory storage in mammals

A structural basis for memory storage in mammals

Protein Phosphatase 2A and Glycogen Synthase Kinase 3 Signaling Modulate Prepulse Inhibition of the Acoustic Startle Response by Altering Cortical M-Type Potassium Channel Activity

Cholinergic innervation in adult rat cerebral cortex: A quantitative immunocytochemical description

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