Neuromodulation, theta rhythm and rat spatial navigation

Hasselmo, Michael E.; Hay, Jonathan; Ilyn, M.; Gorchetchnikov, Anatoli

doi:10.1016/s0893-6080(02)00057-6

Cited by 157 publications

(107 citation statements)

References 62 publications

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“…1 Summary of experimental design and timeline treated rats without naltrexone reflect enduring effects of DFP exposure on compromising hippocampal function. The hippocampus receives acetylcholinergic input from the medial septum and studies show that the ability to remember spatial location is mediated by cholinergic activity within the hippocampus [28]. It is quite possible that the DFP-induced memory deficits observed in these rats affected hippocampal place cells to encode the spatial location of the target platform properly.…”

Section: Discussionmentioning

confidence: 99%

Chronic Treatment with Naltrexone Prevents Memory Retention Deficits in Rats Poisoned with the Sarin Analog Diisopropylfluorophosphate (DFP) and Treated with Atropine and Pralidoxime

2015

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Humans and rats poisoned with sarin develop chronic neurological disabilities that are not prevented with standardized antidotal therapy. We hypothesized that rats poisoned with the sarin analogue diisopropylfluorophosphate (DFP) and resuscitated with atropine and pralidoxime would have long-term memory deficits that were preventable with naltrexone treatment. Long Evans rats (250-275 g) were randomized to: DFP (N=8): single subcutaneous (SC) injection of DFP (5 mg/kg). Treatment (N=9): DFP (5 mg/kg) followed by chronic naltrexone (5 mg/kg/day × 12 weeks). Control (N= 12): single SC injection of isopropyl alcohol, (DFP vehicle) followed by chronic naltrexone (5 mg/kg/day). If toxicity developed after injection, antidotal therapy was initiated with atropine (2 mg/kg) and pralidoxime (25 mg/kg) and repeated as needed. After 12 weeks, rats underwent testing for place learning (acquisition) across 5 days of training using the Morris Water Maze. On day 6 a memory retention test was performed. Statistical analysis was performed using IBM SPSS Statistics. Rats receiving DFP rapidly developed toxicity requiring antidotal rescue. No differences in acquisition were seen between the DFP vs. DFP+naltrexone rats. During memory testing, DFP-poisoned rats spent significantly less time (29.4±2.11 versus 38.5±2.5 s, p<0.05) and traveled less distance (267±24.6 versus 370±27.5 cm, p<0.05) in the target quadrant compared to the treatment group. Treatment rats performed as well as control rats (p>0.05) on the test for memory retention. Poisoning with DFP induced impaired memory retention. Deficits were not prevented by acute rescue with atropine and pralidoxime. Chronic naltrexone treatment led to preserved memory after DFP poisoning.

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Section: Discussionmentioning

confidence: 99%

Chronic Treatment with Naltrexone Prevents Memory Retention Deficits in Rats Poisoned with the Sarin Analog Diisopropylfluorophosphate (DFP) and Treated with Atropine and Pralidoxime

2015

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“…Lesions to the thalamus and the mammillary bodies impact the electrophysiological regulation of the hippocampus (Kirk & Mackay, 2003;Leranth, Carpi, Buzsaki, & Kiss, 1999;Vertes et al, 2004), supporting the idea that lesions of the diencephalon impair hippocampal functioning during behaviorally relevant states. However, cholinergic input from the MS/DB is important for normal hippocampal functioning (Hasselmo, Hay, Ilyn, & Gorchetchnikov, 2002;Sotty et al, 2003) and thiamine deficiency leads to ChAT-positive cell loss in the MS/DB (Pitkin & Savage, 2001,2004) and a loss of fibers in the hippocampus (Nakagawasai et al, 2000). ACh neurons are particularly vulnerable to neuroinflammation and neurodegeneration (Hartig et al, 2002;Wenk & Willard, 1998) and such states are produced during thiamine deficiency (Todd & Butterworth, 1999).…”

Section: Discussionmentioning

confidence: 99%

Blunted hippocampal, but not striatal, acetylcholine efflux parallels learning impairment in diencephalic-lesioned rats

Roland

Savage

2007

Neurobiology of Learning and Memory

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A rodent model of diencephalic amnesia, pyrithiamine-induced thiamine deficiency (PTD), was used to investigate the dynamic role of hippocampal and striatal acetylcholine (ACh) efflux across acquisition of a nonmatching-to-position (NMTP) T-maze task. Changes in ACh efflux were measured in rats at different time points in the acquisition curve of the task (early= day 1, middle = day 5, and late = day 10). Overall, the control group had higher accuracy scores than the PTD group in the latter sessions of NMTP training. During the three microdialysis sampling points, all animals displayed significant increases in ACh efflux in both hippocampus and striatum, while performing the task. However, on day 10, the PTD group showed a significant behavioral impairment that paralleled their blunted hippocampal-but not striatal-ACh efflux during maze training. The results support selective diencephalic-hippocampal dysfunction in the PTD model. This diencephalichippocampal interaction appears to be critical for successful episodic and spatial learning/memory.

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“…Striatal ACh increase associated with cocaine acquisition Crespo et al, 2006;Mark et al, 1999) Striatal ACh alters cocaine-induced locomotor sensitization Hikida et al, 2001Hikida et al, , 2003 mACh receptors decrease after chronic cocaine (Lipton et al, 1995;Macedo et al, 2004;Wilson et al, 1994;Zeigler et al, 1991) Amygdala mAChR may facilitate acquisition of associative learning underlying context-dependent sensitization Itzhak and Martin, 2000) Explicit memory Hippocampus ACh involved in the encoding of new information (Hasselmo and Fehlau, 2001;Hasselmo et al, 2002) Hippocampal ACh increases following cocaine use (Imperato et al, 1993a(Imperato et al, , b, 1996Smith et al, 2004a, b) Conditioned learning VTA VTA ACh involved in conditioned learning (Bechara and van der Kooy, 1989;Museo and Wise, 1994;Olmstead and Franklin, 1993) M 5 -deficient rats decrease cocaine-induced CPP (Fink-Jensen et al, 2003) Striatum Striatal ACh involved in conditioned learning (Legault et al, 2006) NAc ACh inhibits cocaine-induced CPP (Hikida et al, 2001 ACh antagonist blocks induction of locomotor sensitization to cocaine-induced CPP (Itzhak and Martin, 2000) Amygdala Amygdalar ACh facilitates conditioned learning (McIntyre et al, 1998;Power et al, 2003) Amygdalar ACh alters cocaine-induced conditioned learning (See et al, 2003;Zeigler et al, 1991) Attention PFC Elevated ACh may focus attentional resources toward salient stimuli (Baxter and Chiba, 1999;Robbins, 2002;Sarter et al, 2003) Cocaine-addicted subjects show impaired attention (Horner et al, 1996;Jovanovski et al, 2005) Set shifting PFC ACh involved in set shifting (Ragozzino and Choi...…”

Section: Overview Of Animal Models Of Addictionmentioning

confidence: 99%

“…Hippocampal ACh is projected from the septum and nucleus of the diagonal band (McKinney et al, 1983), and DA transmission at D 1 and/or D 2 receptors can enhance hippocampal ACh output (Imperato et al, 1993b). Drugs that block mAChRs, such as scopolamine, impair the encoding of new information (Hasselmo and Fehlau, 2001;Hasselmo et al, 2002) and depletion of ACh is linked to memory disorders such as Alzheimer's disease Quirion et al, 1989). Hippocampal ACh is theorized to facilitate the encoding of new information by simultaneously suppressing excitatory synaptic transmission and enhancing long-term potentiation, while leaving excitatory feed-forward synapses relatively unaffected (Hasselmo et al, 2002).…”

Section: Acetylcholine and Explicit Memorymentioning

confidence: 99%

“…Drugs that block mAChRs, such as scopolamine, impair the encoding of new information (Hasselmo and Fehlau, 2001;Hasselmo et al, 2002) and depletion of ACh is linked to memory disorders such as Alzheimer's disease Quirion et al, 1989). Hippocampal ACh is theorized to facilitate the encoding of new information by simultaneously suppressing excitatory synaptic transmission and enhancing long-term potentiation, while leaving excitatory feed-forward synapses relatively unaffected (Hasselmo et al, 2002). ACh also modulates synaptic plasticity within the hippocampus (Colgin et al, 2003) and long-term potentiation is drastically reduced in genetically engineered mice lacking the mACh M 2 receptor (Seeger et al, 2004).…”

Section: Acetylcholine and Explicit Memorymentioning

confidence: 99%

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The Role of Acetylcholine in Cocaine Addiction

Williams

Adinoff²

2007

Neuropsychopharmacol

160

138

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Central nervous system cholinergic neurons arise from several discrete sources, project to multiple brain regions, and exert specific effects on reward, learning, and memory. These processes are critical for the development and persistence of addictive disorders. Although other neurotransmitters, including dopamine, glutamate, and serotonin, have been the primary focus of drug research to date, a growing preclinical literature reveals a critical role of acetylcholine (ACh) in the experience and progression of drug use. This review will present and integrate the findings regarding the role of ACh in drug dependence, with a primary focus on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine administration produces neuroadaptive changes in the striatum. ACh is further involved in the acquisition of conditional associations that underlie cocaine self-administration and context-dependent sensitization, the acquisition of associations in conditioned learning, and drug procurement through its effects on arousal and attention. Long-term cocaine use may induce neuronal alterations in the brain that affect the ACh system and impair executive function, possibly contributing to the disruptions in decision making that characterize this population. These primarily preclinical studies suggest that ACh exerts a myriad of effects on the addictive process and that persistent changes to the ACh system following chronic drug use may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a potential target for pharmacological treatment interventions in cocaine-addicted subjects. However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of the striatal cholinergic interneurons suggest that a precise target of cholinergic manipulation will be required to impact substance use in the clinical population.

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Neuromodulation, theta rhythm and rat spatial navigation

Cited by 157 publications

References 62 publications

Chronic Treatment with Naltrexone Prevents Memory Retention Deficits in Rats Poisoned with the Sarin Analog Diisopropylfluorophosphate (DFP) and Treated with Atropine and Pralidoxime

Chronic Treatment with Naltrexone Prevents Memory Retention Deficits in Rats Poisoned with the Sarin Analog Diisopropylfluorophosphate (DFP) and Treated with Atropine and Pralidoxime

Blunted hippocampal, but not striatal, acetylcholine efflux parallels learning impairment in diencephalic-lesioned rats

The Role of Acetylcholine in Cocaine Addiction

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