title: Muscarinic and nicotinic modulation of thalamo-prefrontal cortex synaptic plasticity [corrected] in vivo.
abstract: The mediodorsal nucleus of the thalamus (MD) is a rich source of afferents to the medial prefrontal cortex (mPFC). Dysfunctions in the thalamo-prefrontal connections can impair networks implicated in working memory, some of which are affected in Alzheimer disease and schizophrenia. Considering the importance of the cholinergic system to cortical functioning, our study aimed to investigate the effects of global cholinergic activation of the brain on MD-mPFC synaptic plasticity by measuring the dynamics of long-term potentiation (LTP) and depression (LTD) in vivo. Therefore, rats received intraventricular injections either of the muscarinic agonist pilocarpine (PILO; 40 nmol/µL), the nicotinic agonist nicotine (NIC; 320 nmol/µL), or vehicle. The injections were administered prior to either thalamic high-frequency (HFS) or low-frequency stimulation (LFS). Test pulses were applied to MD for 30 min during baseline and 240 min after HFS or LFS, while field postsynaptic potentials were recorded in the mPFC. The transient oscillatory effects of PILO and NIC were monitored through recording of thalamic and cortical local field potentials. Our results show that HFS did not affect mPFC responses in vehicle-injected rats, but induced a delayed-onset LTP with distinct effects when applied following PILO or NIC. Conversely, LFS induced a stable LTD in control subjects, but was unable to induce LTD when applied after PILO or NIC. Taken together, our findings show distinct modulatory effects of each cholinergic brain activation on MD-mPFC plasticity following HFS and LFS. The LTP-inducing action and long-lasting suppression of cortical LTD induced by PILO and NIC might implicate differential modulation of thalamo-prefrontal functions under low and high input drive.
authors.affiliation: Department of Neuroscience and Behavioral Sciences, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Lezio Soares
authors.initials: LS
authors.lastname: Bueno-Junior
authors.forename: Cleiton
authors.initials: C
authors.lastname: Lopes-Aguiar
authors.forename: Rafael Naime
authors.initials: RN
authors.lastname: Ruggiero
authors.forename: Rodrigo Neves
authors.initials: RN
authors.lastname: Romcy-Pereira
authors.forename: João Pereira
authors.initials: JP
authors.lastname: Leite
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D018721:Muscarinic Agonists / Q000008:administration & dosage*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000008:administration & dosage; D010862:Pilocarpine / Q000008:administration & dosage; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013788:Thalamus / Q000187:drug effects
chemical_list: D018721:Muscarinic Agonists; D010862:Pilocarpine; D009538:Nicotine