Biology subjects

Brockett, A. T.

Publications and source records attributed to Brockett, A. T..

3 recordsLinked to original sources

bioRxiv2024

Psilocybin biphasically modulates cortical and behavioral activity in mice

Psilocybin is a serotonergic psychedelic believed to have therapeutic potential for neuropsychiatric conditions. Despite well-documented prevalence of perceptual alterations, hallucinations, and synesthesia associated with psychedelic experiences, little is known about how psilocybin affects sensory cortex or alters the activity of neurons in awake animals. To investigate, we conducted 2-photon imaging experiments in auditory cortex of awake mice and video analysis of mouse behavior, both at baseline and during psilocybin treatment. We found biphasic effects of psilocybin on behavioral and cortical activity. A 2 mg/kg dose of psilocybin initially increased behavioral activity and neural responses to sound. 30 minutes post-dose, mice became behaviorally hypoactive and cortical responses to sound decreased, while neural response variance and noise correlations increased. In contrast, neuronal selectivity for auditory stimuli remained stable during psilocybin treatment. Our results suggest that psilocybin modulates the role of intrinsic versus stimulus-driven activity in sensory cortex, while preserving fundamental sensory processing. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=96 SRC="FIGDIR/small/576229v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@154b46aorg.highwire.dtl.DTLVardef@10d961org.highwire.dtl.DTLVardef@2f83d3org.highwire.dtl.DTLVardef@177c81b_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract.C_FLOATNO Summary of psilocybins effect on auditory cortical responses to sound in mice.30 minutes after injecting the inert vehicle saline, typical auditory responses occur within a relatively narrow range of possible amplitudes, i.e., each neurons response variance is weakly correlated with a neighboring neurons response variance. In contrast, 30 minutes after injecting 2 mg/kg of psilocybin, population response variance becomes more correlated between individual neurons, and the range of response amplitudes increases. These findings suggest that psilocybin modulates the role of intrinsic versus stimulus-driven neural activity in sensory perception, which may serve as a basis for auditory hallucination at the level of neuronal micro-circuits. C_FIG

neuroscience↗

bioRxiv2020

Prior cocaine exposure increases firing to immediate reward while attenuating cue and context signals related to reward value in anterior insula

The insula contributes to behavioral control and is disrupted by substance abuse, yet we know little about the neural signals underlying these functions or how they are disrupted after chronic drug self-administration. Here, rats self-administered either cocaine (experimental group) or sucrose (control) for twelve consecutive days. After a one-month withdrawal period, we recorded from anterior insula while rats performed a previously learned reward-guided decision-making task. Cocaine-exposed rats were more sensitive to value manipulations and were faster to respond. These behavioral changes were accompanied by elevated counts of neurons in the insula that increased firing to reward. These neurons also fired more strongly at the start of long delay trials-when a more immediate reward would be expected, and fired less strongly in anticipation of the actual delivery of delayed rewards. Although reward-related firing to immediate reward was enhanced after cocaine self-administration, reward-predicting cue and context signals were attenuated. Significance StatementThe insula plays a clear role in drug-addiction and drug-induced impairments of decision-making, yet there is little understanding of its underlying neural signals. We found that chronic cocaine self-administration reduces cue and context-encoding in insula, while enhancing signals related to immediate reward. These changes in neural activity likely contribute to impaired decision-making and impulsivity observed after drug use.

neuroscience↗

bioRxiv2019

Enduring consequences of perinatal fentanyl exposure in mice

Opioid use by pregnant women is an understudied consequence associated with the opioid epidemic, resulting in a rise in the incidence of neonatal opioid withdrawal syndrome (NOWS), and lifelong neurobehavioral deficits that result from perinatal opioid exposure. There are few preclinical models that accurately recapitulate human perinatal drug exposure, and few focus on fentanyl, a potent synthetic opioid that is a leading driver of the opioid epidemic. To investigate the consequences of perinatal opioid exposure, we administered fentanyl to mouse dams in their drinking water throughout gestation and until litters were weaned at postnatal day (PD) 21. Fentanyl-exposed dams delivered smaller litters, and had higher litter mortality rates compared to controls. Metrics of maternal care behavior were not affected by the treatment, nor were there differences in dams weight or liquid consumption throughout gestation and 21 days postpartum. Twenty-four hours after weaning and drug cessation, perinatal fentanyl-exposed mice exhibited signs of spontaneous somatic withdrawal behavior, and sex-specific weight fluctuations that normalized in adulthood. At adolescence (PD 35) they displayed elevated anxiety-like behaviors and decreased grooming, assayed in the elevated plus maze and sucrose splash tests. Finally, by adulthood (PD 55) they displayed impaired performance in a two-tone auditory discrimination task. Collectively, our findings suggest that perinatal fentanyl exposed mice exhibit somatic withdrawal behavior and changes across the lifespan reminiscent of humans born with NOWS.

neuroscience↗