How do our brains determine whether something is good or bad? How is this computational goal implemented in biological systems? Given the critical importance of valence processing for survival, the ...brain has evolved multiple strategies to solve this problem at different levels. The psychological concept of “emotional valence” is now beginning to find grounding in neuroscience. This review aims to bridge the gap between psychology and neuroscience on the topic of emotional valence processing. Here, I highlight a subset of studies that exemplify circuit motifs that repeatedly appear as implementational systems in valence processing. The motifs I identify as being important in valence processing include (1) Labeled Lines, (2) Divergent Paths, (3) Opposing Components, and (4) Neuromodulatory Gain. Importantly, the functionality of neural substrates in valence processing is dynamic, context-dependent, and changing across short and long timescales due to synaptic plasticity, competing mechanisms, and homeostatic need.
Tye revisits the theoretical concept of valence originating from psychology to the investigation of valence processing in neuroscience. Tye identifies several neural circuit motifs for valence processing to provide a conceptual framework for valence processing on the implementational level.
The basolateral amygdala (BLA) and ventral hippocampus (vHPC) have both been implicated in mediating anxiety-related behaviors, but the functional contribution of BLA inputs to the vHPC has never ...been directly investigated. Here we show that activation of BLA-vHPC synapses acutely and robustly increased anxiety-related behaviors, while inhibition of BLA-vHPC synapses decreased anxiety-related behaviors. We combined optogenetic approaches with in vivo pharmacological manipulations and ex vivo whole-cell patch-clamp recordings to dissect the local circuit mechanisms, demonstrating that activation of BLA terminals in the vHPC provided monosynaptic, glutamatergic inputs to vHPC pyramidal neurons. Furthermore, BLA inputs exerted polysynaptic, inhibitory effects mediated by local interneurons in the vHPC that may serve to balance the circuit locally. These data establish a role for BLA-vHPC synapses in bidirectionally controlling anxiety-related behaviors in an immediate, yet reversible, manner and a model for the local circuit mechanism of BLA inputs in the vHPC.
•Optogenetic inhibition of BLA-vHPC projections reduces anxiety•Optogenetic activation of BLA-vHPC inputs is sufficient to increase anxiety•In vivo and ex vivo evidence shows glutamatergic inputs are monosynaptic•BLA influences vHPC pyramidal cells via direct excitation and indirect inhibition
Felix-Ortiz et al. explore the interaction between the amygdala and other brain regions, assessing the functional contribution of basolateral amygdala inputs to the ventral hippocampus during anxiety-related behaviors in mice. They demonstrate bidirectional modulation of anxiety-related behaviors by these inputs.
Optogenetic tools have provided a new way to establish causal relationships between brain activity and behaviour in health and disease. Although no animal model captures human disease precisely, ...behaviours that recapitulate disease symptoms may be elicited and modulated by optogenetic methods, including behaviours that are relevant to anxiety, fear, depression, addiction, autism and parkinsonism. The rapid proliferation of optogenetic reagents together with the swift advancement of strategies for implementation has created new opportunities for causal and precise dissection of the circuits underlying brain diseases in animal models.
Salient but aversive stimuli inhibit the majority of dopamine (DA) neurons in the ventral tegmental area (VTA) and cause conditioned place aversion (CPA). The cellular mechanism underlying DA neuron ...inhibition has not been investigated and the causal link to behavior remains elusive. Here, we show that GABA neurons of the VTA inhibit DA neurons through neurotransmission at GABAA receptors. We also observe that GABA neurons increase their firing in response to a footshock and provide evidence that driving GABA neurons with optogenetic effectors is sufficient to affect behavior. Taken together, our data demonstrate that synaptic inhibition of DA neurons drives place aversion.
► In the VTA, optogenetic activation of GABA neurons in vivo inhibits DA neurons ► A footshock excites GABA neurons and inhibits of a large majority of DA neurons ► The inhibition of DA neurons by a footshock is GABAA receptor dependent ► Activation of GABA neurons is sufficient to elicit conditioned place aversion
Tan et al. show that footshock induces GABA neuron excitation, leading to GABAA receptor-mediated inhibition of DA neurons. Optogenetic manipulation shows that VTA GABA neurons activation or direct inhibition of DA neurons is sufficient to drive behavioral aversion.
Neural mechanisms of social homeostasis Matthews, Gillian A.; Tye, Kay M.
Annals of the New York Academy of Sciences,
December 2019, Letnik:
1457, Številka:
1
Journal Article
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Odprti dostop
Social connections are vital to survival throughout the animal kingdom and are dynamic across the life span. There are debilitating consequences of social isolation and loneliness, and social support ...is increasingly a primary consideration in health care, disease prevention, and recovery. Considering social connection as an “innate need,” it is hypothesized that evolutionarily conserved neural systems underlie the maintenance of social connections: alerting the individual to their absence and coordinating effector mechanisms to restore social contact. This is reminiscent of a homeostatic system designed to maintain social connection. Here, we explore the identity of neural systems regulating “social homeostasis.” We review findings from rodent studies evaluating the rapid response to social deficit (in the form of acute social isolation) and propose that parallel, overlapping circuits are engaged to adapt to the vulnerabilities of isolation and restore social connection. By considering the neural systems regulating other homeostatic needs, such as energy and fluid balance, we discuss the potential attributes of social homeostatic circuitry. We reason that uncovering the identity of these circuits/mechanisms will facilitate our understanding of how loneliness perpetuates long‐term disease states, which we speculate may result from sustained recruitment of social homeostatic circuits.
Here, we explore the identity of neural systems regulating “social homeostasis.” We review findings from rodent studies evaluating the rapid response to social deficit (in the form of acute social isolation) and propose that parallel, overlapping circuits are engaged to adapt to the vulnerabilities of isolation and restore social connection. By considering the neural systems regulating other homeostatic needs, such as energy and fluid balance, we discuss the potential attributes of social homeostatic circuitry.
The amygdala has long been associated with emotion and motivation, playing an essential part in processing both fearful and rewarding environmental stimuli. How can a single structure be crucial for ...such different functions? With recent technological advances that allow for causal investigations of specific neural circuit elements, we can now begin to map the complex anatomical connections of the amygdala onto behavioural function. Understanding how the amygdala contributes to a wide array of behaviours requires the study of distinct amygdala circuits.
Projections from the lateral hypothalamus (LH) to the ventral tegmental area (VTA), containing both GABAergic and glutamatergic components, encode conditioned responses and control compulsive ...reward-seeking behavior. GABAergic neurons in the LH have been shown to mediate appetitive and feeding-related behaviors. Here we show that the GABAergic component of the LH-VTA pathway supports positive reinforcement and place preference, while the glutamatergic component mediates place avoidance. In addition, our results indicate that photoactivation of these projections modulates other behaviors, such as social interaction and perseverant investigation of a novel object. We provide evidence that photostimulation of the GABAergic LH-VTA component, but not the glutamatergic component, increases dopamine (DA) release in the nucleus accumbens (NAc) via inhibition of local VTA GABAergic neurons. Our study clarifies how GABAergic LH inputs to the VTA can contribute to generalized behavioral activation across multiple contexts, consistent with a role in increasing motivational salience.
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•Activating GABAergic LH-VTA supports positive reinforcement•GABAergic LH-VTA activation inhibits VTA GABA neurons•GABAergic LH-VTA activation increases dopamine release in the NAc•Activating glutamatergic LH-VTA causes avoidance and suppresses DA release in the NAc
Nieh et al. demonstrate that inhibitory inputs from the lateral hypothalamus disinhibit dopamine neurons in the ventral tegmental area to increase motivated behaviors, including approach and social interaction. In contrast, excitatory projections suppress dopamine release and promote avoidance.
Although the basolateral amygdala (BLA) is known to play a critical role in the formation of memories of both positive and negative valence, the coding and routing of valence-related information is ...poorly understood. Here, we recorded BLA neurons during the retrieval of associative memories and used optogenetic-mediated phototagging to identify populations of neurons that synapse in the nucleus accumbens (NAc), the central amygdala (CeA), or ventral hippocampus (vHPC). We found that despite heterogeneous neural responses within each population, the proportions of BLA-NAc neurons excited by reward predictive cues and of BLA-CeA neurons excited by aversion predictive cues were higher than within the entire BLA. Although the BLA-vHPC projection is known to drive behaviors of innate negative valence, these neurons did not preferentially code for learned negative valence. Together, these findings suggest that valence encoding in the BLA is at least partially mediated via divergent activity of anatomically defined neural populations.
•BLA-NAc and BLA-CeA cell populations encode valence distinctly, yet are heterogeneous•More BLA-NAc neurons were excited by the sucrose predictive cue than the BLA overall•More BLA-CeA neurons were excited by the quinine predictive cue than the BLA overall•BLA-vHPC neurons responded to cues of positive and negative valence evenly
Beyeler et al. reveal the real-time neural coding dynamics within the basolateral amygdala to show that neural responses to cues that predict rewarding or aversive outcomes differ depending on the anatomical projection target of each neuronal subpopulation.
Currently there is no general approach for achieving specific optogenetic control of genetically defined cell types in rats, which provide a powerful experimental system for numerous established ...neurophysiological and behavioral paradigms. To overcome this challenge we have generated genetically restricted recombinase-driver rat lines suitable for driving gene expression in specific cell types, expressing Cre recombinase under the control of large genomic regulatory regions (200–300 kb). Multiple tyrosine hydroxylase (
Th)::
Cre and choline acetyltransferase (
Chat)::
Cre lines were produced that exhibited specific opsin expression in targeted cell types. We additionally developed methods for utilizing optogenetic tools in freely moving rats and leveraged these technologies to clarify the causal relationship between dopamine (DA) neuron firing and positive reinforcement, observing that optical stimulation of DA neurons in the ventral tegmental area (VTA) of
Th::
Cre rats is sufficient to support vigorous intracranial self-stimulation (ICSS). These studies complement existing targeting approaches by extending the generalizability of optogenetics to traditionally non-genetically-tractable but vital animal models.
► Generation of
Th::Cre rat lines for targeting dopaminergic and noradrenergic cells ► Generation of
Chat::Cre rat lines suitable for targeting cholinergic neurons ► Methods for optogenetic control of physiology and behavior in freely moving rats ► Stimulation of dopamine neurons supports intracranial self-stimulation in rats
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