Honors & Awards
Walter and Idun Berry Postdoctoral Fellowship, Stanford School of Medicine (2017-2020)
Dean's Postdoctoral Fellowship, Stanford School of Medicine (2017)
Bachelor of Arts, University of Cambridge (2009)
Doctor of Philosophy, Columbia University (2016)
Karl Deisseroth, Postdoctoral Faculty Sponsor
Amygdala-Midbrain Connections Modulate Appetitive and Aversive Learning.
The central amygdala (CeA) orchestrates adaptive responses to emotional events. While CeA substrates for defensive behaviors have been studied extensively, CeA circuits for appetitive behaviors and their relationship to threat-responsive circuits remain poorly defined. Here, we demonstrate that the CeA sends robust inhibitory projections to the lateral substantia nigra (SNL) that contribute to appetitive and aversive learning in mice. CeA→SNL neural responses to appetitive and aversive stimuli were modulated by expectation and magnitude consistent with a population-level salience signal, which was required for Pavlovian conditioned reward-seeking and defensive behaviors. CeA→SNL terminal activation elicited reinforcement when linked to voluntary actions but failed to support Pavlovian associations that rely on incentive value signals. Consistent with a disinhibitory mechanism, CeA inputs preferentially target SNL GABA neurons, and CeA→SNL and SNL dopamine neurons respond similarly to salient stimuli. Collectively, our results suggest that amygdala-nigra interactions represent a previously unappreciated mechanism for influencing emotional behaviors.
View details for DOI 10.1016/j.neuron.2020.03.016
View details for PubMedID 32294466
A mm-Sized Wireless Implantable Device for Electrical Stimulation of Peripheral Nerves
IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS
2018; 12 (2): 257–70
A wireless electrical stimulation implant for peripheral nerves, achieving >10× improvement over state of the art in the depth/volume figure of merit, is presented. The fully integrated implant measures just 2 mm × 3 mm × 6.5 mm (39 mm3, 78 mg), and operates at a large depth of 10.5 cm in a tissue phantom. The implant is powered using ultrasound and includes a miniaturized piezoelectric receiver (piezo), an IC designed in 180 nm HV BCD process, an off-chip energy storage capacitor, and platinum stimulation electrodes. The package also includes an optional blue light-emitting diode for potential applications in optogenetic stimulation in the future. A system-level design strategy for complete operation of the implant during the charging transient of the storage capacitor, as well as a unique downlink command/data transfer protocol, is presented. The implant enables externally programmable current-controlled stimulation of peripheral nerves, with a wide range of stimulation parameters, both for electrical (22 to 5000 μA amplitude, ∼14 to 470 μs pulse-width, 0 to 60 Hz repetition rate) and optical (up to 23 mW/mm2 optical intensity) stimulation. Additionally, the implant achieves 15 V compliance voltage for chronic applications. Full integration of the implant components, end-to-end in vitro system characterizations, and results for the electrical stimulation of a sciatic nerve, demonstrate the feasibility and efficacy of the proposed stimulator for peripheral nerves.
View details for DOI 10.1109/TBCAS.2018.2799623
View details for Web of Science ID 000428547600001
View details for PubMedID 29578414
Basolateral amygdala circuitry in positive and negative valence.
Current opinion in neurobiology
2018; 49: 175–83
All organisms must solve the same fundamental problem: they must acquire rewards and avoid danger in order to survive. A key challenge for the nervous system is therefore to connect motivationally salient sensory stimuli to neural circuits that engage appropriate valence-specific behavioral responses. Anatomical, behavioral, and electrophysiological data have long suggested that the amygdala plays a central role in this process. Here we review experimental efforts leveraging recent technological advances to provide previously unattainable insights into the functional, anatomical, and genetic identity of neural populations within the amygdala that connect sensory stimuli to valence-specific behavioral responses.
View details for PubMedID 29525574
Manipulating neural activity in physiologically classified neurons: triumphs and challenges
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
2015; 370 (1677)
Understanding brain function requires knowing both how neural activity encodes information and how this activity generates appropriate responses. Electrophysiological, imaging and immediate early gene immunostaining studies have been instrumental in identifying and characterizing neurons that respond to different sensory stimuli, events and motor actions. Here we highlight approaches that have manipulated the activity of physiologically classified neurons to determine their role in the generation of behavioural responses. Previous experiments have often exploited the functional architecture observed in many cortical areas, where clusters of neurons share response properties. However, many brain structures do not exhibit such functional architecture. Instead, neurons with different response properties are anatomically intermingled. Emerging genetic approaches have enabled the identification and manipulation of neurons that respond to specific stimuli despite the lack of discernable anatomical organization. These approaches have advanced understanding of the circuits mediating sensory perception, learning and memory, and the generation of behavioural responses by providing causal evidence linking neural response properties to appropriate behavioural output. However, significant challenges remain for understanding cognitive processes that are probably mediated by neurons with more complex physiological response properties. Currently available strategies may prove inadequate for determining how activity in these neurons is causally related to cognitive behaviour.
View details for DOI 10.1098/rstb.2014.0216
View details for Web of Science ID 000360552100015
View details for PubMedID 26240431
Neural Representations of Unconditioned Stimuli in Basolateral Amygdala Mediate Innate and Learned Responses
2015; 162 (1): 134-145
Stimuli that possess inherently rewarding or aversive qualities elicit emotional responses and also induce learning by imparting valence upon neutral sensory cues. Evidence has accumulated implicating the amygdala as a critical structure in mediating these processes. We have developed a genetic strategy to identify the representations of rewarding and aversive unconditioned stimuli (USs) in the basolateral amygdala (BLA) and have examined their role in innate and learned responses. Activation of an ensemble of US-responsive cells in the BLA elicits innate physiological and behavioral responses of different valence. Activation of this US ensemble can also reinforce appetitive and aversive learning when paired with differing neutral stimuli. Moreover, we establish that the activation of US-responsive cells in the BLA is necessary for the expression of a conditioned response. Neural representations of conditioned and unconditioned stimuli therefore ultimately connect to US-responsive cells in the BLA to elicit both innate and learned responses.
View details for DOI 10.1016/j.cell.2015.06.027
View details for Web of Science ID 000357542300015
View details for PubMedID 26140594
Antagonism at NMDA receptors, but not beta-adrenergic receptors, disrupts the reconsolidation of pavlovian conditioned approach and instrumental transfer for ethanol-associated conditioned stimuli
2012; 219 (3): 751-761
Reconsolidation is the process by which memories require restabilisation following destabilisation at retrieval. Since even old, well-established memories become susceptible to disruption following reactivation, treatments based upon disrupting reconsolidation could provide a novel form of therapy for neuropsychiatric disorders based upon maladaptive memories, such as drug addiction. Pavlovian cues are potent precipitators of relapse to drug-seeking behaviour and influence instrumental drug seeking through at least three psychologically and neurobiologically distinct processes: conditioned reinforcement, conditioned approach (autoshaping) and conditioned motivation (pavlovian-instrumental transfer or PIT). We have previously demonstrated that the reconsolidation of memories underlying the conditioned reinforcing properties of drug cues depends upon NMDA receptor (NMDAR)- and β-adrenergic receptor (βAR)-mediated signalling. However, it is unknown whether the drug cue memory representations underlying conditioned approach and PIT depend upon the same mechanisms.Using orally self-administered ethanol as a reinforcer in two separate experiments, we investigated whether the reconsolidation of the memories underlying conditioned approach and PIT requires βAR- and NMDAR-dependent neurotransmission.For ethanol self-administering but non-dependent rats, the memories underlying conditioned approach and PIT for a pavlovian drug cue were disrupted by the administration of the NMDAR antagonist MK-801, but not the administration of the βAR antagonist propranolol, when given in conjunction with memory reactivation.As for natural reinforcers, NMDARs are required for the reconsolidation of all aspects of pavlovian drug memories, but βARs are only required for the memory representation underlying conditioned reinforcement. These results indicate the potential utility of treatments based upon disrupting cue-drug memory reconsolidation in preventing relapse.
View details for DOI 10.1007/s00213-011-2399-9
View details for Web of Science ID 000299175800006
View details for PubMedID 21766171