ライフサイエンスコーパス: cholinergic

1 analysis reveals that the numbers of pontine cholinergic (259,578) and noradrenergic (127,752) neuron

2 ons, but the receptor and cellular bases for cholinergic actions are just beginning to be understood.

3 0], provides a potential method of improving cholinergic activation [11, 12].

4 While acute M-current inhibition via cholinergic activation or direct channel block made neur

5 ments confirmed that the effects depended on cholinergic activation.

6 ne injections to the SCN, demonstrating that cholinergic activity at the SCN is necessary for arousal

7 loss of CHT-dependent activation of cortical cholinergic activity in STs degrades top-down executive

8 Alteration of cholinergic activity produced a reduction in the frequen

9 Indeed, bypassing cholinergic activity with a clinically tested alpha7nACh

10 er behavior, which requires frontal cortical cholinergic activity.

11 astrointestinal (GI) and cardiovascular (CV) cholinergic adverse events (AEs) previously attributed t

12 ies in rats and dogs and was found to induce cholinergic AEs and convulsion at therapeutic indices si

13 ric modulation of M1 is sufficient to elicit cholinergic AEs.

14 Bn, surrounding the presynaptic terminals of cholinergic afferent fibers from projection neurons (Pn)

15 physiologic and pathologic responses to the cholinergic agonist carbachol (Cch) and cholecystokinin

16 r systemic or intrastriatal injection of the cholinergic agonist oxotremorine.

17 We investigated responses to cholinergic agonist treatment vs. neurostimulation by el

18 frequency of Ca(2+) oscillations induced by cholinergic agonist was lowered by more than 30%.

19 ministration of oxotremorine, an unselective cholinergic agonist, Gnal(+/-) mice developed more abnor

20 Cholinergic alterations in dementia with Lewy bodies (DL

21 Our results confirm the existence in DLB of cholinergic alterations, reaching both cortical and subc

22 ighlight a novel mechanism by which striatal cholinergic and cannabinoid signaling leads to sustained

23 tters profile showed a significant effect on cholinergic and dopaminergic systems.

24 clusters, but a pre-synaptic segregation of cholinergic and glutamatergic release sites is also poss

25 The distribution of cholinergic and noncholinergic neurons projecting to the

26 we examined the topographic organization of cholinergic and noncholinergic projections from the BF t

27 posterior commissure, supernumerary pontine cholinergic and noradrenergic cells, and an enlarged per

28 izures, accompanied by expression changes in cholinergic and TGFBR2 pathways as well as in miR-134.

29 These findings reveal that glutamatergic, cholinergic, and GABAergic PPT neurons differentially in

30 We identified multiple monoaminergic, cholinergic, and peptidergic cell types linked to alertn

31 Although previous studies suggest that cholinergic antagonists would worsen pathophysiology, th

32 The cholinergic anthelmintics had different selectivities fo

33 regulating the inflammatory response via the cholinergic anti-inflammatory pathway (CAP).

34 I and prevent CKD by stimulating the splenic cholinergic anti-inflammatory pathway.

35 tero inflammation via an endogenous cerebral cholinergic anti-inflammatory pathway.

36 vagus nerve stimulation (VNS) activates the cholinergic antiinflammatory pathway (CAP), resulting in

37 The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate an

38 the postganglionic motoneurons in the CG are cholinergic, as are their inputs, there is evidence from

39 tion was involved in context switching, with cholinergic axons increasing activity during behavior an

40 We found that LDT cholinergic axons selectively enhanced the bursting acti

41 In animal models, development of the cholinergic basal forebrain (cBF) is selectively vulnera

42 While muscarinic cholinergic blockade prevented the VNS-induced bradycard

43 r triggering relapse and the human cognitive-cholinergic capacity for the processing of such cues, go

44 ACh synthesis, that accounts for attenuated cholinergic capacity in STs.

45 The synchronous rhythmic activation of cholinergic cells drives the coordinated arrests of all

46 l number, density, and soma volume of septal cholinergic cells, which were visualized in brain sectio

47 Cholinergic ChAT-ir neurons were also found within trans

48 ere we report the contribution of a specific cholinergic circuit to this computation.

49 ding for cocaine through the activation of a cholinergic circuit, and they suggest that LHb dysfuncti

50 anding of the development and maintenance of cholinergic circuits is limited, as the factors regulati

51 We found that cholinergic circuits modulate appetite suppression on do

52 However, the mechanism by which cholinergic circuits shape signal processing in the audi

53 eurotrophic factor conditions operates under cholinergic constraint that is mediated by muscarinic re

54 olinergic receptor blockade to delineate the cholinergic contributions to prefrontal oscillations dur

55 we aimed to assess whether ameliorating this cholinergic deficit with the acetylcholinesterase inhibi

56 ays included genes involved in serotonergic, cholinergic, dopaminergic, GABAergic, and glutamergic sy

57 mical, and network-level mechanisms for this cholinergic-dopaminergic interplay.

58 Cholinergic dysfunction at the level of MGB may affect s

59 Additionally, a cholinergic dysregulated mouse model overexpressing a mi

60 These cholinergic effects may provide a neurobiological mechan

61 two successive synaptic relays in a simple, cholinergic efferent pathway.

62 Little is known about the function of the cholinergic efferents innervating peripheral vestibular

63 dro-beta-erythroidine, suggests that loss of cholinergic efficacy may also be the result of an age-re

64 Here we demonstrate that cholinergic enhancement improves detection of a target f

65 However, the consequences of cholinergic enhancement on visuospatial perception in hu

66 However, the influence of cholinergic enhancement on visuospatial perception remai

67 We found that cholinergic enhancement with the cholinesterase inhibito

68 Unlike cholinergic enhancement, dopamine (bromocriptine) and no

69 We propose that the blunted cholinergic excitability contributes to the functional m

70 Here, we show that cholinergic excitation of commissural layer 5 mPFC pyram

71 We demonstrate that cholinergic excitation promotes calcium entry at subthre

72 It was found that the density of cholinergic fiber varicosities was higher in epileptic r

73 the wakefulness-dependent activity of septal cholinergic fibers through the alpha7-nicotinic acetylch

74 To visualize the cholinergic fibers, we used brain sections immunostained

75 Our data offer new insights into cholinergic function by revealing the temporally orchest

76 Knockdown of cholinergic function in a subset of these sublateral neu

77 uired for the formation of processes and for cholinergic function of sublateral motor neurons, which

78 mpathetic neurons prevented the induction of cholinergic genes after MI, suggesting that inflammatory

79 c cell populations, and the precise roles of cholinergic, glutamatergic, and GABAergic PPT cell group

80 experiments in the present study reveal that cholinergic, glutamatergic, and GABAergic PPT neurons ea

81 ontains at least three different cell types (cholinergic, glutamatergic, and gamma-aminobutyric acid

82 lopment of drugs for alleviating symptoms of cholinergic hypofunction in patients with advanced Alzhe

83 renia, a disorder characterized by NMDAR and cholinergic hypofunctions.

84 A novel, inherited nicotinic cholinergic inflammatory effect exists in young SHR, mea

85 GABA receptors in rRPa does not mediate the cholinergic inhibition of BAT SNA.

86 KEY POINTS: A tonically active, muscarinic cholinergic inhibition of rostral raphe pallidus (rRPa)

87 Cholinergic inhibitory responses depend on calcium relea

88 The PFC receives significant cholinergic innervation and nicotinic acetylcholine rece

89 lopontine tegmental nucleus is the source of cholinergic innervation for sensory thalamus and is a cr

90 is not surprising that deficits in cortical cholinergic innervation have been correlated with loss o

91 ts the potential significance of subcortical cholinergic innervation in the evolution of the human br

92 Here, we show that disrupting cholinergic innervation of GABAergic neurons in the C. e

93 Cholinergic innervation of the basal ganglia is importan

94 Cholinergic innervation, as measured by axon and interne

95 ugh a modulated expression of SOCS3, whereas cholinergic innervation-mediated suppression of NK cell

96 deficits due to a disruption of hippocampal cholinergic innervation.

97 Photostimulation of endogenous cholinergic input (1) enhances firing of putative BLA pr

98 sulting hemodynamic signals, chronic loss of cholinergic input resulted in dramatic impairments in bo

99 The cortical cholinergic input system, via phasic increases in prefro

100 e and energy expenditure are influenced by a cholinergic input to neurons in the rostral raphe pallid

101 The tonically active cholinergic input to rRPa originates caudal to the hypot

102 VLM is not the sole source of the muscarinic cholinergic input to rRPa.

103 The precise underlying circuitry of this cholinergic input to the main olfactory bulb remains unc

104 These findings suggest that cholinergic input to the MGB increases the strength of t

105 We conclude that a tonically active cholinergic input to the rRPa inhibits BAT SNA via activ

106 The dopamine neurons receive cholinergic input via nicotinic acetylcholine receptors

107 nterneuron population integrates centrifugal cholinergic input with broadly tuned feedforward sensory

108 form layer, where they integrate centrifugal cholinergic input with highly convergent feedforward sen

109 Our findings provide novel insights on how cholinergic inputs to subregions of the SNc regulate the

110 Cholinergic inputs to the MGB appear to maximize sensory

111 acetylcholine receptor (nAChR) activation by cholinergic inputs.

112 We sought to uncover the impact of striatal cholinergic interneuron (SCIN) degeneration on persevera

113 rily mediated by acetylcholine released from cholinergic interneurons (ChIs) acting locally in the st

114 and shown to require synchronized firing of cholinergic interneurons (CINs) and activation of nicoti

115 Cholinergic interneurons (CINs) drive dopamine release t

116 glia, including a reduced number of striatal cholinergic interneurons (SCIN), are involved in their p

117 opamine (DA) release evoked by activation of cholinergic interneurons displays a high degree of summa

118 icotinic input constitutes a major output of cholinergic interneurons remains unknown.

119 c parvalbumin or nitric oxide-expressing and cholinergic interneurons were normal in Hdc KO mice.

120 ) independent on the spontaneous activity of cholinergic interneurons, and (3) that cocaine increased

121 cholinergic pathways-as well as the striatal cholinergic interneurons.

122 s dopamine tone without altering activity of cholinergic interneurons.

123 ergic neurons in the SNpc or dorsal striatal cholinergic interneurons.

124 els in D1 medium spiny neurons as well as in cholinergic interneurons.

125 d a disynaptic, nicotinic excitation through cholinergic interneurons.

126 our results indicate a critical role for the cholinergic Ipc in this gating process.

127 Increasing cholinergic levels in the cortex through optogenetic sti

128 Ts than STs and this effect was abolished by cholinergic losses despite the fact that all rats contin

129 gonists was mimicked by intra-LHb muscarinic cholinergic (mACh) antagonist injection, and activation

130 that iuGC-rats have long-lasting changes in cholinergic markers in the LDT, together with a decrease

131 we sought to determine whether an analogous cholinergic mechanism underlies menin's synaptogenic fun

132 diated slow excitation is also attributed to cholinergic mechanisms.

133 IHCs) receive inhibitory efferent input from cholinergic medial olivocochlear (MOC) neurons originati

134 ous pressure and impaired non-adrenergic non-cholinergic-mediated relaxation in the penis, consistent

135 entified miR-211 as a putative attenuator of cholinergic-mediated seizures by intersecting forebrain

136 Parallel processing of cholinergic modulation by cortical interneurons therefor

137 inhibition of distinct Sst interneurons and cholinergic modulation determined their in vivo activity

138 fore, our results point to the importance of cholinergic modulation in mPFC for trace conditioning an

139 Our results suggest that cholinergic modulation may contribute to attention by ac

140 The loss of excitatory cholinergic modulation may play a critical role in mPFC

141 showed that, 1 week after the nerve injury, cholinergic modulation of layer 5 (L5) pyramidal neurons

142 In addition to demonstrating cholinergic modulation of naturally-evoked and behaviora

143 Cholinergic modulation was involved in context switching

144 ar modification is observed under heightened cholinergic modulation.

145 Cholinergic motor neuron classes of the ventral nerve co

146 ncreased excitability and a normal number of cholinergic motor neuron synapses, indicating a compensa

147 lcium channel subunits [Cacna1c and Cacnb2], cholinergic muscarinic receptor 4 [Chrm4)], dopamine rec

148 dentified an age-related mechanism along the cholinergic nerve-airway smooth muscle (ASM) axis that u

149 ult mice, elevated the level and activity of cholinergic nerves (termed neuroplasticity).

150 Our findings suggest that reduced levels of cholinergic neuromodulation can mediate an attentional b

151 itulated in mice with pan-neuron-specific or cholinergic neuron-specific ablation of the cpeb2 gene.

152 eal that GABAergic signaling is regulated by cholinergic neuronal activity, probably through distinct

153 Cholinergic neuronal loss co-occurs, particularly within

154 es at 12 months of age, these mice developed cholinergic neuronal loss in the basal forebrain, GABAer

155 precise contributions of the medial septum's cholinergic neurones to these functions remain unknown.

156 modulating the excitability of medial septal cholinergic neurones.

157 ion that destroyed 40-50% of basal forebrain cholinergic neurons and later, after extinction training

158 This is mainly because of the cholinergic neurons contained in the PPT nucleus.

159 s the PD patients had significantly more PPN cholinergic neurons containing mtDNA deletion levels exc

160 h optogenetic stimulation of basal forebrain cholinergic neurons decreases the dependency that is com

161 We isolated single cholinergic neurons from postmortem PPNs of aged control

162 we propose that the PPN and, in particular, cholinergic neurons have a central role in updating the

163 Degeneration of cholinergic neurons in aging and Alzheimer's dementia is

164 Cholinergic neurons in the basal forebrain project heavi

165 istribution of glutamatergic, GABAergic, and cholinergic neurons in the brain of the African cichlid

166 of neurons surround Bar: rostral-dorsomedial cholinergic neurons in the laterodorsal tegmental nucleu

167 duced by selective optogenetic activation of cholinergic neurons in the nucleus accumbens (NAc) are i

168 on of this inhibitory olfactory microcircuit.Cholinergic neurons innervate multiple layers in the mai

169 Striatal cholinergic neurons integrate cognitive and motivational

170 -related neuroplasticity of septohippocampal cholinergic neurons is capable of increasing neuronal ex

171 gic neurons of the substantia nigra (SN) and cholinergic neurons of the dorsal motor nucleus of the v

172 of hearing, descending (efferent) input from cholinergic neurons originating in the brainstem inhibit

173 Specific deletion of 5-HT1B from cholinergic neurons results in impaired inhibition of AC

174 Here the authors show that VGLUT3(+) cholinergic neurons selectively innervate deep short axo

175 ouse gastrointestinal tract co-localize with cholinergic neurons that express the neuropeptide neurom

176 rmined the effects of dynorphin-A on MCPO/SI cholinergic neurons using patch-clamp recordings in brai

177 that orexin-A and -B excite basal forebrain cholinergic neurons, but orexin-producing neurons also m

178 ic area, but there was no innervation by the cholinergic neurons.

179 emonstrate a functional relationship between cholinergic neuroplasticity and ASM contractile phenotyp

180 We demonstrated that cholinergic neuroplasticity is necessary for the inducti

181 its memory formation by helping to terminate cholinergic neurotransmission at the Pn:MBn synapse.

182 We show that cholinergic neurotransmission encodes the oscillatory se

183 The septohippocampal cholinergic neurotransmission has long been implicated i

184 These effects were not due to cholinergic neurotransmission, persisted during partial

185 Our study reveals how cholinergic neurotransmission, which can represent senso

186 tatory (nicotinic or glutamatergic) mediated cholinergic neurotransmission.

187 than STs and that this would require intact cholinergic neurotransmission.

188 medial and lateral SNc neurons modulated by cholinergic neurotransmission.

189 Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere

190 ed in Tg(mglur6b:EGFP)zh1 constitute a novel cholinergic, non-GABAergic, non-starburst amacrine cell

191 -sphincter-muscle contraction via excitatory cholinergic parasympathetic innervation [1, 2].

192 le itself may express melanopsin [5], or its cholinergic parasympathetic innervation may be modulated

193 ly induced seizures alongside changes in the cholinergic pathway genes, implicating this miR in the a

194 scle contractility via neural and non-neural cholinergic pathways in the colon, the involvement of th

195 minatocortical), and the Ch5 (pontothalamic) cholinergic pathways-as well as the striatal cholinergic

196 e in vivo in DLB the integrity of the 3 main cholinergic pathways-the Ch1 (septohippocampal), the Ch4

197 for inhibitory glutamatergic and excitatory cholinergic/peptidergic drives in the absence of food.

198 Both the number of septal cells with cholinergic phenotype and their density were increased i

199 okines induce the transient acquisition of a cholinergic phenotype in cardiac sympathetic neurons.

200 tional experiments yielded no glycinergic or cholinergic positive cells in the IC, and descending pro

201 Activation of cholinergic PPT neurons suppressed lower-frequency elect

202 ffects have been linked with the activity of cholinergic PPT neurons, the PPT also includes interming

203 acute stress attenuated IRI by activating a cholinergic, predominantly sympathetic, anti-inflammator

204 Here, we identify a specific basal forebrain cholinergic projection that innervates select neurons co

205 ce imaging studies suggesting extra-striatal cholinergic projections from the pedunculopontine nucleu

206 iculate body (MGB) is regulated, in part, by cholinergic projections from the pontomesencephalic tegm

207 While cholinergic receptor activation has long been known to d

208 triggered by depolarizing stimuli following cholinergic receptor activation.

209 We iontophoretically applied the general cholinergic receptor agonist carbachol onto neurons in d

210 ed the selective expression of the nicotinic cholinergic receptor alpha2 (Chrna2) in mice to genetica

211 ignaling, neurophysiological recordings, and cholinergic receptor blockade to delineate the cholinerg

212 In pancreatic beta cells, muscarinic cholinergic receptor M3 (M3R) stimulates glucose-induced

213 In addition, early intervention with cholinergic receptor muscarinic (ChRM)-3 blocker reverse

214 mpared with neuronal nicotinic acetylcholine cholinergic receptors (nAChRs) assembled from alpha and

215 fects on performance of cognitive tasks, and cholinergic receptors are being actively explored as pro

216 Muscarinic and nicotinic cholinergic receptors both contributed specifically to g

217 Here, we stimulated cholinergic receptors in prefrontal cortex and examined

218 Stimulation of cholinergic receptors is being explored to create cognit

219 amine signaling, these data suggest that NAc cholinergic receptors may gate the expression of cue-mot

220 Cholinergic regulation of dopaminergic inputs into the s

221 ynaptogenic actions of menin are specific to cholinergic regulation.

222 E was accelerated and gastric ICC and phasic cholinergic responses were increased.

223 Here we examine the interaction of these two cholinergic responses with respect to their contribution

224 Cholinergic "retinal waves" are initiated in starburst a

225 Serotonin inhibits the cholinergic rhythm, and increases ciliary beat frequency

226 We identified cholinergic, serotonergic, and catecholaminergic ciliomo

227 bsequent depolarizing steps, suggesting that cholinergic signal transduction itself is not voltage-se

228 provide insights into the connection between cholinergic signaling and visual attention.

229 However, the relationship between cholinergic signaling during cue detection and neural ac

230 yrrolate, we confirm the role for muscarinic cholinergic signaling in pathogenesis using additional p

231 In contrast, acute genetic disruption of cholinergic signaling in the adult circuit does not repr

232 To examine whether cholinergic signaling in the SNc controls mouse behavior

233 These findings reveal mechanisms by which cholinergic signaling influences visual spatial interact

234 ed two experiments to test whether enhancing cholinergic signaling selectively alters perceptual meas

235 n the nervous system that modulate nicotinic cholinergic signaling, but their functions and specifici

236 Here we combined subsecond measures of cholinergic signaling, neurophysiological recordings, an

237 iption factors involved in neurogenesis, and cholinergic signalling molecules, several of which are s

238 ereby maintaining the fidelity of inhibitory cholinergic signalling.

239 as indirectly through feedforward GABAergic/cholinergic signals mediated by starburst amacrine cells

240 These cholinergic signals were coincident with increased neuro

241 We report that fidelity of cholinergic SK responses requires the continued presence

242 factor for sporadic MCI/AD, display impaired cholinergic sprouting after EC lesion.

243 The cholinergic sprouting is gender dependent and highly sen

244 CHGA360-373) selectively inhibited nicotinic cholinergic stimulated catecholamine release from chroma

245 Moreover, cholinergic stimulation attenuated saccade direction sel

246 Surprisingly, cholinergic stimulation decreased neurons' ability to di

247 Cholinergic stimulation disrupted rule selectivity regar

248 In addition, cholinergic stimulation excited putative pyramidal neuro

249 Cholinergic stimulation has been shown to have beneficia

250 Our results suggest excessive cholinergic stimulation has detrimental effects on DLPFC

251 Cholinergic stimulation induces parasympathetic neuro-im

252 We hypothesized that cholinergic stimulation of PFC during performance of a c

253 Cholinergic stimulation of the gastric epithelium induce

254 We previously reported that cholinergic stimulation with pyridostigmine (PY) induces

255 ity of neuromodulation of cerebral cortex by cholinergic stimulation, an area of active exploration w

256 development of ASM hypercontractility after cholinergic stimulation.

257 Central cholinergic structures within the brain of the even-toed

258 ansmembrane transport, TGFBR2 signaling, and cholinergic synapse pathways.

259 re, we show that the capacity of presynaptic cholinergic synapses to respond to stimulation by elevat

260 acetylcholine at both central and peripheral cholinergic synapses, including the neuromuscular juncti

261 E) is crucial for degrading acetylcholine at cholinergic synapses.

262 rosophila are likely stored as plasticity of cholinergic synapses.

263 pment, the relative amounts of GABAergic and cholinergic synaptic drive shift dendrites between diffe

264 calized Dmca1D channels, which activate upon cholinergic synaptic input and amplify EPSPs, thus indic

265 imulation (TBS) that alleviates the decay in cholinergic synaptic transmission effectively protects a

266 D mice are in part caused by degeneration of cholinergic synaptic transmission that modulates the dNG

267 amyloid-beta plaques similar to AD patients, cholinergic synaptic transmission, dNGI survival and spa

268 Data suggest that cholinergic system abnormalities may play a relevant rol

269 addition, we assessed the involvement of the cholinergic system in cognitive and neuropsychiatric dis

270 tural reorganization of the septohippocampal cholinergic system in experimental epilepsy, involving f

271 e present findings indicate that the central cholinergic system in the miniature pig is similar to ot

272 with an inadequate adaptive response of the cholinergic system in the RV.

273 dies of neurodegenerative diseases where the cholinergic system is compromised.

274 nal drug availability and that the forebrain cholinergic system mediates such vulnerability.

275 whether these effects were selective to the cholinergic system or would also be observed following e

276 ear that immune cells express a non-neuronal cholinergic system, which is stimulated in the course of

277 cognitive enhancers based on stimulating the cholinergic system.

278 In auditory cortex, cholinergic systems have been shown to increase salience

279 tylcholine (ACh), but the functional role of cholinergic systems in adult mammalian peripheral sensor

280 xperimental epilepsy on the areal density of cholinergic terminals (fiber varicosities) in the dentat

281 ions of interest, including the striatum and cholinergic terminals in Ch1 (hippocampus), Ch4 (cortica

282 The concomitant sprouting of cholinergic terminals in the hippocampus has been propos

283 e behaving mice and found that activation of cholinergic terminals in the medial SNc decreased locomo

284 ced by cocaine was not due to an increase in cholinergic tone and is likely a product of an increase

285 AMP pathway in association with an increased cholinergic tone creates alterations in striatal neuron

286 Modifying septal cholinergic tone in this way also led mice to exhibit be

287 To investigate the mechanism by which cholinergic tone regulates hnRNPA2/B1 expression, we use

288 Generating cholinergic transients in conjunction with cues enhanced

289 e, we evaluate how GABA inhibition modulates cholinergic transmission and its involvement during tast

290 The results show that reduced cholinergic transmission in medial prefrontal cortex (mP

291 Alterations in cholinergic transmission in the anterior cingulate corte

292 Further investigation revealed that cholinergic transmission in the KO dorsal motor nucleus

293 In the central nervous system (CNS), cholinergic transmission induces synaptic plasticity tha

294 neuronal DIRAS1 gene with a proposed role in cholinergic transmission provides not only a candidate f

295 s disease (AD) is whole-body upregulation of cholinergic transmission via inhibition of acetylcholine

296 lator circuits, most notably those involving cholinergic transmission, appears to be correlated with

297 inical benefit in diseases showing defective cholinergic transmission, such as AD.

298 consensus report on physical urticarias and cholinergic urticaria (Allergy, 2009).

299 caria, heat urticaria, vibratory angioedema, cholinergic urticaria, contact urticaria, and aquagenic

300 We demonstrate that cholinergic wave patterns are dictated by recurrent conn