Hannah M. Batchelor's research while affiliated with Yale-New Haven Hospital and other places

Publications (19)

Article
Full-text available
Experimental research controls for past experience, yet prior experience influences how we learn. Here, we tested whether we could recruit a neural population that usually encodes rewards to encode aversive events. Specifically, we found that GABAergic neurons in the lateral hypothalamus (LH) were not involved in learning about fear in naïve rats....
Article
Background: In response to the COVID-19 pandemic, the Yale New Haven Health System began rescheduling nonurgent outpatient appointments as virtual visits in March 2020. While Yale New Haven Health expanded its telemedicine infrastructure to accommodate this shift, many appointments were delayed and patients faced considerable uncertainty. Objecti...
Article
Full-text available
The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and activity of neurons expressing CaMKIIα (a marker for glutamatergic principal cells) in mice during cue-reward learning using a fl...
Article
Full-text available
The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and activity of neurons expressing CaMKIIα (a marker for glutamatergic principal cells) in mice during cue-reward learning using a fl...
Article
Full-text available
The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and activity of neurons expressing CaMKIIα (a marker for glutamatergic principal cells) in mice during cue-reward learning using a fl...
Preprint
Full-text available
The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and principal neuron activity in mice during cue-reward learning using a fluorescent ACh sensor and calcium indicators. We found that...
Article
Full-text available
Dopamine neurons are proposed to signal the reward prediction error in model-free reinforcement learning algorithms. This term represents the unpredicted or ‘excess’ value of the rewarding event, value that is then added to the intrinsic value of any antecedent cues, contexts or events. To support this proposal, proponents cite evidence that artifi...
Preprint
Full-text available
Dopamine neurons fire transiently in response to unexpected rewards. These neural correlates are proposed to signal the reward prediction error described in model-free reinforcement learning algorithms. This error term represents the unpredicted or excess value of the rewarding event. In model-free reinforcement learning, this value is then stored...
Article
Full-text available
In the version of this article initially published, the laser activation at the start of cue X in experiment 1 was described in the first paragraph of the Results and in the third paragraph of the Experiment 1 section of the Methods as lasting 2 s; in fact, it lasted only 1 s. The error has been corrected in the HTML and PDF versions of the article...
Article
Full-text available
Pharmacologic treatment with the neuropeptide neurotensin (Nts) modifies motivated behaviors such as feeding, locomotor activity, and reproduction. Dopamine (DA) neurons of the ventral tegmental area (VTA) control these behaviors, and Nts directly modulates the activity of DA neurons via Nts receptor-1. While Nts sources to the VTA have been descri...
Article
Full-text available
The central mechanism by which neurotensin (Nts) potentiates weight loss has remained elusive. We leveraged chemogenetics to reveal that Nts-expressing neurons of the lateral hypothalamic area (LHA) promote weight loss in mice by increasing volitional activity and restraining food intake. Intriguingly, these dual weight loss behaviors are mediated...
Article
Sensory preconditioning has been used to implicate midbrain dopamine in modelbased learning, contradicting the view that dopamine transients reflect model-free value. However, it has been suggested that model-free value might accrue directly to the preconditioned cue through mediated learning. Here, building on previous work (Sadacca et al., 2016),...
Article
Full-text available
Sensory preconditioning has been used to implicate midbrain dopamine in model-based learning, contradicting the view that dopamine transients reflect model-free value. However, it has been suggested that model-free value might accrue directly to the preconditioned cue through mediated learning. Here, building on previous work (Sadacca et al., 2016)...
Article
Full-text available
Midbrain dopamine neurons have been proposed to signal prediction errors as defined in model-free reinforcement learning algorithms. While these algorithms have been extremely powerful in interpreting dopamine activity, these models do not register any error unless there is a difference between the value of what is predicted and what is received. Y...
Article
Full-text available
Dopamine (DA) neurons in the ventral tegmental area (VTA) are heterogeneous and differentially regulate ingestive and locomotor behaviors that affect energy balance. Identification of which VTA DA neurons mediate behaviors that limit weight gain has been hindered, however, by the lack of molecular markers to distinguish VTA DA populations. Here, we...
Article
Full-text available
Associative learning is driven by prediction errors. Dopamine transients correlate with these errors, which current interpretations limit to endowing cues with a scalar quantity reflecting the value of future rewards. We tested whether dopamine might act more broadly to support learning of an associative model of the environment. Using sensory prec...

Citations

... During pre-exposure, we delivered light into the brain (470 nm, 1 s, 20 Hz) at the onset of the cue. We have previously used a greater number of pre-exposure trials to generate successful latent inhibition 58 . We used less pre-exposure here as we wanted to give an opportunity to see either an enhancement or reduction in latent inhibition in our experimental group. ...
... The methods were adapted from (56) to measure in vivo calcium signals as fractional changes of fluorescence (dF/F), using a standard 2-lenses-1-site 405/465-nm fiber photometry system. The console controlled two connectorized LEDs (CLEDs; 405 nm modulated at 208 Hz and 465 nm modulated at 572 Hz). ...
... Technological advances have refined our understanding, revealing that ACh can signal over a range of timescales, providing mechanisms for both fast and slow signaling, determined by several factors including location within the brain, mechanism of release, and type of synaptic contact (Disney and Higley, 2020). Disruptions to this normal cholinergic transmission are thought to contribute to a number of neuropsychiatric disorders (Higley and Picciotto, 2014;Sarter et al., 1999) and lead to altered behavior in rodents (Crouse et al., 2020;Hersman et al., 2017;Jiang et al., 2016). ...
... More recent work has attempted to explain dopamine release dynamics by incorporating the effects of temporal uncertainty to explain dopamine release seen in multistage operant tasks. While dopamine and other neuromodulators are released in response to aversive as well as rewarding cues (Crouse et al., 2020;Hangya et al., 2015;Matsumoto & Hikosaka, 2009;Rajebhosale et al., 2021;Sturgill et al., 2020), the neuromodulatory basis of aversive prediction errors remains poorly understood. NE has been proposed to have a variety of computational roles in inference, particularly as a representation of uncertainty, salience, and attention (O'Donnell et al., 2012;Yu & Dayan, 2005). ...
... Furthermore, rather than glutamatergic deficits being distinct from dopaminergic hyperfunction, the present findings show how glutamatergic deficits can directly lead to dopaminergic hyperfunction [2,45]. Thus, by increasing DA signals to environmental cues and generating inappropriate levels of attention such that stimuli remain "as if novel" when they would otherwise habituate, GluA1 dysfunction effectively increases the window of contiguity which increases the likelihood that associations will form between cues [46,47]. In this way, GluA1 dysfunction provides a mechanism through which maladaptive associations could be formed between stimuli and events that would otherwise be perceived as unrelated, and thus for generating delusional beliefs. ...
... doi: bioRxiv preprint first posted online Jul. 26, 2019; and the phenomenon is likely to be much more multifaceted than this model suggests. First, phasic dopamine 342 signalling to hippocampus may encode other kinds of prediction errors or aspects of reward to which the VTA is 343 sensitive (Keiflin et al. 2019;Sharpe et al. 2019;Takahashi et al. 2017), and bias replay by the same mechanism. ...
... Along this line, the locomotor effects observed could be mediated by the neuropeptide neurotensin, whose kinetics are slower 39 than the neurotransmitter GABA. Of note, neurotensin receptor type 1 (Ntsr1) was reported to regulate energy expenditure and locomotor behavior in the SNc/ventral tegmental area complex 40 , and we and others showed that neurotensin-expressing neurons in the IPAC project to this area 41 . Another possibility is that IPAC Nts neurons are heterogeneous, such that some are involved in controlling hedonic eating and others are involved in regulating physical activities. ...
... Within the adult brain, NtsR1 is expressed within the cingulate cortex, midbrain, subiculum and in the hindbrain (Kessler et al., 1987;Moyse et al., 1987;Najimi et al., 2014), but the roles of NtsR1 in these regions may differ. Indeed, activating site-specific Nts-or NtsR1-expressing neurons can modulate physiology ranging from social interaction, locomotor activity, feeding and drinking (McHenry et al., 2017;Woodworth et al., 2017b;Kurt et al., 2019;Perez-Bonilla et al., 2021). Given the temporal and site-specific expression of NtsR1, it is imperative to systematically examine its role within discrete neuronal populations and at different stages of life. ...
... We thus focused on sensory preconditioning protocols with trial-specific associative learning 68 tasks (Brogden, 1939). This paradigm typically consists of two stages: two neutral events (i.e., direct 69 and indirect events) are paired together in an initial learning phase, and then the direct event is 70 paired with a salient stimulus (i.e., threat or reward) ----namely an emotional or reward learning 71 phase (Kurth-Nelson et al., 2015;Sharpe et al., 2017; Wong et al., 2019). Animal work has shown 72 that the salient stimulus can spread its value to the indirect neutral event through an integration 73 mechanism (Holmes et al., 2018;Sadacca et al., 2018;Sharpe et al., 2017). ...
... One possibility is that S2 elicits a CR at the time of test through an associative chain. In this case, presentation of S2 activates the representation of S1, which activates the representation of the US (Rescorla and Cunningham, 1978;Rescorla and Freberg, 1978;Sharpe et al., 2017a). A second possibility is that during S1-US pairings, S1 retrieves the memory of S2, allowing S2 to become associated with the US through mediated conditioning (Rescorla and Cunningham, 1978;Rescorla and Freberg, 1978;Wong et al., 2019). ...