Cortical computations emerge from the dynamics of neurons embedded in complex cortical circuits. Within these circuits, neuronal ensembles, which represent subnetworks with shared functional connectivity, emerge in an experience-dependent manner. Here we induced ensembles in
Ethanol tolerance is the first type of behavioral plasticity and neural plasticity that is induced by ethanol intake, and yet its molecular and circuit bases remain largely unexplored. Here, we characterize the following three distinct forms of ethanol tolerance in male
- NSF-PAR ID:
- 10407518
- Publisher / Repository:
- DOI PREFIX: 10.1523
- Date Published:
- Journal Name:
- The Journal of Neuroscience
- Volume:
- 43
- Issue:
- 12
- ISSN:
- 0270-6474
- Page Range / eLocation ID:
- p. 2210-2220
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
ex vivo cortical circuits from mice of either sex by differentially activating subpopulations through chronic optogenetic stimulation. We observed a decrease in voltage correlation, and importantly a synaptic decoupling between the stimulated and nonstimulated populations. We also observed a decrease in firing rate during Up-states in the stimulated population. These ensemble-specific changes were accompanied by decreases in intrinsic excitability in the stimulated population, and a decrease in connectivity between stimulated and nonstimulated pyramidal neurons. By incorporating the empirically observed changes in intrinsic excitability and connectivity into a spiking neural network model, we were able to demonstrate that changes in both intrinsic excitability and connectivity accounted for the decreased firing rate, but only changes in connectivity accounted for the observed decorrelation. Our findings help ascertain the mechanisms underlying the ability of chronic patterned stimulation to create ensembles within cortical circuits and, importantly, show that while Up-states are a global network-wide phenomenon, functionally distinct ensembles can preserve their identity during Up-states through differential firing rates and correlations.SIGNIFICANCE STATEMENT The connectivity and activity patterns of local cortical circuits are shaped by experience. This experience-dependent reorganization of cortical circuits is driven by complex interactions between different local learning rules, external input, and reciprocal feedback between many distinct brain areas. Here we used anex vivo approach to demonstrate how simple forms of chronic external stimulation can shape local cortical circuits in terms of their correlated activity and functional connectivity. The absence of feedback between different brain areas and full control of external input allowed for a tractable system to study the underlying mechanisms and development of a computational model. Results show that differential stimulation of subpopulations of neurons significantly reshapes cortical circuits and forms subnetworks referred to as neuronal ensembles. -
It is generally understood that the main role of the cerebellum is in movement planning and coordination, but neuroimaging has led to striking findings of its involvement in many aspects of cognitive processing. Mental visualization is such a cognitive process, extensively involved in learning and memory, artistic and inventive creativity, etc. Here, our aim was to conduct a multidimensional study of cerebellar involvement in the non-motor cognitive tasks. First, we used fMRI to investigate whether the cognitive task of visualization from an immediate memory of complex spatial structures (line drawings) engages the cerebellum, and identified a cerebellar network of both strongly activated and suppressed regions. Second, the task-specificity of these regions was examined by comparative analysis with the task of perceptual exploration and memorization of the drawings to be later visualized from memory. BOLD response patterns over the iterations of each task differed significantly; unexpectedly, the suppression grew markedly stronger in visualization. Third, to gain insights in the organization of these regions into cerebellar networks, we determined the directed inter-regional causal influences using Granger Causal Connectivity analysis. Additionally, the causal interactions of the cerebellar networks with a large-scale cortical network, the Default Mode Network (DMN), were studied. Fourth, we investigated rapid cognitive learning in the cerebellum at the level of short-term BOLD response evolution within each region of interest, and at the higher level of network reorganization. Our paradigm of interleaved sequences of iteration between two tasks combined with some innovative analyses were instrumental in addressing these questions. In particular, rapid forms of non-motor learning that strongly drive cerebellar plasticity through mental visualization were uncovered and characterized at both sub-lobular and network levels. Collectively, these findings provide novel and expansive insights into high-order cognitive functions in the cerebellum, and its macroscale functional neuroanatomy. They represent a basis for a framework of rapid cerebellar reorganization driven by non-motor learning, with implications for the enhancement of cognitive abilities such as learning and memory.more » « less
-
Abstract 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 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 like 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 abstinence in a mouse model of chronic THC exposure. 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 to THC. Altered striatal DA release, sleep, and affect-related behaviors associated with spontaneous THC abstinence were more consistently observed in male mice. These findings provide a foundation for preclinical study of directly translatable non-precipitated THC withdrawal symptoms and the neural mechanisms that affect them.more » « less
-
more » « less
Background Aversion to the orosensory properties of concentrated ethanol (EtOH) solutions is often cited as a primary barrier to initiation of drinking and may contribute to abstention. These aversive properties include gustatory processes which encompass both bitter‐like taste qualities and trigeminal‐mediated irritation. Chronic intermittent EtOH access (
CIA ) results in substantial and persistent increases in EtOH consumption, but the degree to which this facilitation involves sensory responding to EtOH and other bitter stimuli is currently undetermined.Methods Long‐Evans rats were given brief‐access licking tests designed to examine the immediate, taste‐guided assessment of the palatability of EtOH and quinine solutions. Rats were assessed once in a naïve state and again following previous brief‐access exposure, or following 4 weeks of
CIA . The relationship between the sensitivity to the aversive orosensory properties of EtOH and quinine following EtOH access and the impact of antecedent quinine exposure on the acceptance of EtOH were determined in 2 parallel studies.Results Both brief access to EtOH and 4‐week
CIA resulted in substantial rightward shifts in the concentration–response function of brief‐access EtOH licking, indicating that EtOH exposure increased acceptance of the taste of EtOH. The initial sensitivity to the aversive orosensory properties of EtOH and quinine was positively correlated in naïve rats, such that rats that were initially more accepting of quinine were also more accepting of EtOH. Rats that sampled quinine immediately prior to tasting EtOH exhibited successive positive contrast in that they were more accepting of highly concentrated EtOH, relative to a water‐control group.Conclusions Increased EtOH acceptance following exposure is, at least in part, facilitated by a decrease in its aversive sensory properties. Both long‐ and short‐term access increase the palatability of the taste of EtOH in brief‐access licking tests. Moreover, the sensitivity to the bitterness of quinine was predictive of acceptance of EtOH indicating some commonality in the sensory mechanisms that mediate the initial acceptance of the 2 stimuli. Accordingly, immediate prior exposure to quinine results in increased acceptance of EtOH, suggesting that successive positive contrast between oral stimuli may contribute to increased alcohol consumption.
-
Animals employ diverse learning rules and synaptic plasticity dynamics to record temporal and statistical information about the world. However, the molecular mechanisms underlying this diversity are poorly understood. The anatomically defined compartments of the insect mushroom body function as parallel units of associative learning, with different learning rates, memory decay dynamics and flexibility (Aso and Rubin, 2016). Here, we show that nitric oxide (NO) acts as a neurotransmitter in a subset of dopaminergic neurons in Drosophila. NO’s effects develop more slowly than those of dopamine and depend on soluble guanylate cyclase in postsynaptic Kenyon cells. NO acts antagonistically to dopamine; it shortens memory retention and facilitates the rapid updating of memories. The interplay of NO and dopamine enables memories stored in local domains along Kenyon cell axons to be specialized for predicting the value of odors based only on recent events. Our results provide key mechanistic insights into how diverse memory dynamics are established in parallel memory systems.more » « less
