Long-Term Shaping of Corticostriatal Synaptic Activity by Acute Fasting.

Barbara Picconi,Valeria Calabrese,Federica Campanelli,Gioia Marino,Paolo Calabresi,Laura Petrosini,Daniela Laricchiuta,Veronica Ghiglieri,Giuseppina Natale

doi:10.3390/ijms22041916

Abstract

Food restriction is a robust nongenic, nonsurgical and nonpharmacologic intervention known to improve health and extend lifespan in various species. Food is considered the most essential and frequently consumed natural reward, and current observations have demonstrated homeostatic responses and neuroadaptations to sustained intermittent or chronic deprivation. Results obtained to date indicate that food deprivation affects glutamatergic synapses, favoring the insertion of GluA2-lacking α-Ammino-3-idrossi-5-Metil-4-idrossazol-Propionic Acid receptors (AMPARs) in postsynaptic membranes. Despite an increasing number of studies pointing towards specific changes in response to dietary restrictions in brain regions, such as the nucleus accumbens and hippocampus, none have investigated the long-term effects of such practice in the dorsal striatum. This basal ganglia nucleus is involved in habit formation and in eating behavior, especially that based on dopaminergic control of motivation for food in both humans and animals. Here, we explored whether we could retrieve long-term signs of changes in AMPARs subunit composition in dorsal striatal neurons of mice acutely deprived for 12 hours/day for two consecutive days by analyzing glutamatergic neurotransmission and the principal forms of dopamine and glutamate-dependent synaptic plasticity. Overall, our data show that a moderate food deprivation in experimental animals is a salient event mirrored by a series of neuroadaptations and suggest that dietary restriction may be determinant in shaping striatal synaptic plasticity in the physiological state.

Highlights

Dietary restriction and acute food deprivation are voluntary practices currently used in many cultures for religious and health reasons [1,2,3]
Based on previous findings showing that food deprivation may impact glutamatergic synapses through enhancement of GluA2-lacking Ammino-3-idrossi-5-Metil-4-idrossazol-Propionic Acid receptors (AMPARs)-mediated activity in inhibitory neurons [25], we explored whether in spiny projection neurons (SPNs) of mice acutely deprived for 12 hours/day, for two consecutive days, we could retrieve signs of the synaptic insertion of GluA2-lacking AMPARs
To explore the long-term effects of acute food restriction on the activity of striatal SPNs, we first analyzed the basal membrane properties through ex vivo patch-clamp and intracellular recordings from SPNs in corticostriatal slices obtained from 40-days-old Food Restricted (FR) and aged-matched C57BL/6J male mice (Naïve) (Figure 1A)

Summary

Introduction

Dietary restriction and acute food deprivation (fasting) are voluntary practices currently used in many cultures for religious and health reasons [1,2,3]. Other studies reported a compensatory upregulation of D1 Dopamine (DA) receptors [14,15] with enhanced phosphorylation of the glutamatergic AMPAR GluA1 at Ser845 This downstream effect increases peak current, facilitates the trafficking to the cell surface [16,17,18] and stabilizes the membrane Ca2+permeable AMPARs [19]. In cells expressing these receptors, a combination of fast decay kinetics and large conductances that enhance synaptic transmission create the conditions for metaplasticity, in which the synapses become primed for a preferential direction of plasticity [20,21]. We analyzed the glutamatergic neurotransmission and the principal forms of DA-and glutamate-dependent synaptic plasticity: the corticostriatal long-term depression (LTD) and LTP

Results

Animals

Slices Preparation

Whole-cell Patch-clamp Recordings

Intracellular Recordings with Sharp Electrodes

Chemicals

Statistical Analyses