Biology subjects

Mateo, Y.

Publications and source records attributed to Mateo, Y..

4 recordsLinked to original sources

bioRxiv2022

Gestational Ethanol Exposure Induces Sex-specific Striatal Acetylcholine and Dopamine Deficits

Fetal alcohol exposure has deleterious consequences on the cognitive abilities and motor skills of patients affected by Fetal Alcohol Spectrum Disorder (FASD) and in pre-clinical models of gestational ethanol exposure (GEE). Deficits in striatal cholinergic and dopamine function impair action learning and execution, yet the effects of GEE on striatal acetylcholine and dopamine release remain unexplored. Here, we report that ethanol (EtOH) exposure during the first ten postnatal days (GEEP0-P10), which mimics EtOH consumption during the last gestational trimester in humans, induces enduring sex-specific anatomical and motor learning deficits in female mice. These behavioral impairments were accompanied by increased evoked-dopamine levels in the dorsolateral striatum (DLS) of GEEP0-P10 female, but not male, mice. Further experiments revealed impaired striatal {beta}2-containing nicotinic acetylcholine receptor (nAChRs)-modulation of electrically evoked dopamine release. Using a genetically encoded acetylcholine sensor (GACh3.0), we found a reduced decay of acetylcholine transients in DLS of GEEP0-P10 females in the presence of an acetylcholinesterase inhibitor galantamine. Finally, we showed that this effect is associated with decreased excitability of striatal cholinergic interneurons (CINs), pointing to activity-dependent defects in acetylcholine release. Altogether, these data shed a new light on striatal deficits that might underlie cognitive and motor learning symptoms of patients affected by FASD.

neuroscience↗

bioRxiv2022

Sub-second striatal dopamine dynamics assessed by simultaneous fast-scan cyclic voltammetry and fluorescence biosensor

Dopamine produces neuromodulation throughout the basal ganglia, cortex and other brain regions, and is implicated in movement control, neural mechanisms of reward and actions of misused substances. The efferent projections of dopaminergic neurons with somata in the substantia nigra pars compacta and ventral tegmental area strongly innervate different striatal subregions. While much is known about the function of these neurons, there is a relative deficiency of information about in vivo dopamine dynamics in the nigrostriatal projections, especially those to the dorsolateral striatum (DLS). In past studies, subsecond dopamine changes were measured predominantly with fast-scan cyclic voltammetry (FSCV) both in brain slices and in vivo. However, traditional FSCV has limitations in discriminating among catecholamines, and cannot be used for simultaneous measurement of both slow and fast/phasic dopamine changes. In addition, FSCV has been most useful for measuring dopamine in the ventral striatum in vivo with less utility for measurement in dorsolateral striatum. The development of genetically encoded dopamine sensors has provided a new approach to measuring slow and fast dopamine dynamics both in brain slices and in vivo, raising the hope of more facile measurement of in vivo dopamine measurements, including in areas where measurement was previously difficult with FSCV. To this end, we first evaluated dLight photometry in brain slices with simultaneous FSCV. We found that both techniques yielded comparable findings. However, differences were noted in responses to dopamine transporter inhibitors, including cocaine. We then used in vivo fiber photometry with dLight to examine responses to cocaine in DLS and compared responses during Pavlovian conditioning in DLS to two other striatal subregions. These experiments show that dopamine increases are readily detectable in DLS and provide new information about dopamine transient kinetics and slowly developing signaling during conditioning. Overall, our findings indicate that dLight photometry is well suited to measuring dopamine dynamics in a striatal region of great interest where such measurements were difficult previously.

neuroscience↗

bioRxiv2021

Sex-dependent changes in murine striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence

Withdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studies have examined withdrawal symptoms following exposure to delta-9-tetrahydrocannabinol (THC), difficulties in obtaining objective measures of spontaneous withdrawal using paradigms that mimic cessation of use in humans have slowed research. The neuromodulator dopamine (DA) is known to be affected by chronic THC treatment and plays a role in many behaviors related to human THC withdrawal symptoms. These symptoms include sleep disturbances that often drive relapse, and emotional behaviors, e.g., irritability and anhedonia. We examined THC withdrawal-induced changes in striatal DA release and the extent to which sleep disruption and behavioral maladaptation manifest during withdrawal in a mouse chronic cannabis exposure model. Using a THC treatment regimen known to produce tolerance we measured electrically elicited DA release in acute brain slices from different striatal subregions during early and late THC abstinence. Long-term polysomnographic recordings from mice were used to assess vigilance state and sleep architecture before, during, and after THC treatment. We additionally assessed how behaviors that model human withdrawal symptoms are altered by chronic THC treatment in early and late abstinence. We detected altered striatal DA release, sleep disturbances that mimic clinical observations, and behavioral maladaptation in mice following tolerance inducing THC treatment. Sex differences were observed in nearly all metrics. Altered striatal DA release, sleep and affect-related behaviors associated with spontaneous THC abstinence were more consistently observed in male mice. To our knowledge these findings provide the first model of directly translatable non-precipitated cannabis withdrawal symptoms, in particular, sleep disruption.

neuroscience↗

bioRxiv2019

Operant self-stimulation of thalamic terminals in the dorsomedial striatum is constrained by metabotropic glutamate receptor 2

Dorsal striatal manipulations including stimulation of dopamine release and activation of medium spiny neurons (MSNs) are sufficient to drive reinforcement-based learning. Glutamatergic innervation of the dorsal striatum by both the cortex and thalamus is a critical determinant of both MSN activity and local regulation of dopamine release. However, the relationship between glutamatergic inputs to the striatum and behavioral reinforcement is not well understood. We sought to evaluate the reinforcing properties of optogenetic stimulation of thalamostriatal terminals, which are associated with vesicular glutamate transporter 2 (Vglut2) expression, in the dorsomedial striatum (DMS), a region implicated in goal-directed operant behaviors. In mice expressing channelrhodopsin-2 (ChR2) under control of the Vglut2 promoter, brief optical stimulation of the DMS reinforces operant lever-pressing behavior. Mice also acquire operant self-stimulation of thalamic terminals in the DMS when ChR2 expression is virally targeted to the intralaminar thalamus. Because the presynaptic G protein-coupled receptor metabotropic glutamate receptor 2 (mGlu2) robustly inhibits glutamate and dopamine release induced by activation of thalamostriatal afferents, we examined the regulation of thalamostriatal self-stimulation by mGlu2. We find that administration of an mGlu2/3 agonist or an mGlu2-selective positive allosteric modulator reduces self-stimulation. In contrast, blockade of these receptors increases thalamostriatal self-stimulation, suggesting that endogenous activation of these receptors negatively modulates the reinforcing properties of thalamostriatal activity. These findings demonstrate that stimulation of thalamic terminals in the DMS is sufficient to reinforce a self-initiated action, and that thalamostriatal reinforcement is constrained by mGlu2 activation.

neuroscience↗