Research

Research Vision for Future Lab

I am a systems neuroscientist specializing in the electrophysiological basis of cognition, using neurodevelopmental disorders (NDDs) as a lens on its building blocks. NDDs that cause intellectual disability provide insight into the essential cortical circuits underlying cognition, but patients often cannot complete complex laboratory tasks. Field potentials, the summed activity of many neurons, are amenable measures because they can be recorded task-free by electroencephalography (EEG). Oscillatory and non-oscillatory field potential activity is known to change with healthy development and cognition. While excitation-inhibition (E:I) imbalance is a leading hypothesis into disruptions of field potential activity in NDDs, the cells and circuits that produce these disruptions, and what they imply for cognition, remains unclear. My background in electrophysiology, circuit dissection, and reward-guided behaviors positions me to test how field potentials relate to the physiological building blocks of cognition, using a reverse translation approach from human EEG to patient-derived tissue and mouse behaviors (Figure 1). By tracing a human EEG feature to its cellular origin and testing its relationship to behavior in healthy and disrupted neurodevelopment, my work will advance understanding of how cortical circuits support cognition and identify candidate readouts of treatment response.

In the near term, my research program will test in patient-derived tissue whether the EEG signature associated with cognitive profile in people with intellectual disability is carried by their own cortical cells (Focus 1) and determine in a MECP2 mutant mouse model which cell types produce it (Focus 2). In the long term, we will test whether restoring gene function in those cell types restores both the signature and innate cognitive behaviors (Focus 3).

Postdoctoral Research with Dr. Bradley Voytek

Neurodevelopmental disorders are linked to cortical excitation-inhibition (E:I) imbalance, yet objective readouts of this dysfunction across human and experimental models, and means to trace them to specific cell types, have not been established. My postdoctoral work in Dr. Bradley Voytek’s lab develops such readouts from the neural power spectrum. In a double-blind, placebo-controlled crossover trial of purified cannabidiol (CBD) in autistic boys, I showed that aperiodic EEG measures tracked CBD blood metabolite levels, which correlated with receptive vocabulary, nonverbal intelligence, and visuomotor coordination, supporting their role as treatment-responsive biomarkers (Cazares et al., 2026a). In 276 neurotypical adults followed over five years, I found that the aperiodic exponent declined and tracked slowing on a sustained attention task, a
domain-specific marker of attentional aging (Cazares et al., 2026b). In human iPSC derived cultures on multi-electrode arrays, I co-led work showing that nested oscillations emerge over development, are reduced by GABA-A receptor blockade, arise earlier with more GABAergic neurons, and are reshaped by potassium-channel and cholinergic manipulation, establishing a tractable, E:I-dependent model of human oscillogenesis (Pré, Cazares et al., 2026). I also reviewed how stem cell-derived neural tissue can disentangle the mechanisms of aperiodic activity (Cazares and Voytek, 2026). To connect such signatures to cellular origins, I contributed data to a protocol for START, which pairs monosynaptic rabies tracing with single-nucleus RNA sequencing to map the cell types providing inputs to defined neurons (Patiño et al., 2026). Together, these tools ground my proposed program to extend spectral biomarkers and cell-type methods to broader NDDs.

• Cazares C, Rigby L, Kang L, Getzmann S, Arnau S, Wascher E, Voytek B. (2026) Aperiodic EEG activity is a domain-specific marker of attentional aging in neurotypical adults. Journal of Neuroscience. https://doi.org/10.1523/JNEUROSCI.1306-26.2026
• Cazares C, Voytek B. (2026) Disentangling the mechanisms of aperiodic neural activity using pluripotent stem cell derived neural tissue models. (In Proofs at Journal of Neurophysiology)
• Patino M, Bhamidipati SK, Cazares C, Callaway EM. (2026) Protocol for mapping neural circuit connectivity with START: Single transcriptome assisted rabies tracing. STAR Protoc. 2026 Jun 19;7(2):104634. doi: 10.1016/j.xpro.2026.104634. PMID: 42284148; PMCID: PMC13309977.
• Pr D*, Cazares C*, Wooten A.T., Zhou H, Onofre I, Neil A, Logan T, Hu R, Lui J.H., Voytek B and Bang A.G. (2026) Pharmacological manipulation of nested oscillations in human iPSC-derived 2D neuronal networks. Neurobiol Dis. 2026 Jan 24;220:107281. doi: 10.1016/j.nbd.2026.107281.
• Cazares C, Hutton A, Trauner D, Voytek B. (2026) Cannabidiol blood metabolite levels after cannabidiol treatment are associated with broadband EEG changes and improvements in visuomotor and non-verbal cognitive abilities in boys with autism requiring higher levels of support. Transl Psychiatry 16, 109.
  https://doi.org/10.1038/s41398-026-03815-y

Postdoctoral Research with Dr. Kay Tye

Throughout the animal kingdom, social species establish social hierarchies and use social rank to guide the appropriate expression of dominance behaviors that are critical for survival. Neurobiological investigations have identified a key role for medial prefrontal cortex to lateral hypothalamus projection circuits in representing social ranks and mediating the expression of social dominance behaviors. The orbitofrontal cortex (OFC) has also been shown to process social information. OFC processes are thought to be mediated by vast neuromodulatory innervation from subcortical structures known to regulate sociability, such as the dorsal raphe nucleus (DRN). Serotonergic (5-HT) DRN neurons have been identified as a key neural substrate for mediating social interaction behaviors and they provide the majority of serotonergic innervation to the OFC. However, it is unclear whether DRN^5-HT-OFC circuits can process social ranking information to influence behaviors dictated by social ranks.

By using state-of-the-art techniques measuring the granularity of innate behaviors and associated neural activity in freely moving animals, my work aimed to bridge a substantial gap between the computational roles of neurons and their ability to govern social cognition. To this end, we developed a novel assay to model competition for prey between members of an established social hierarchy. Our assay takes into consideration ethologically-relevant phenomena in which 1) dominant mice have priority access to resources in social contexts and 2) mice display flexible predatory behaviors in their pursuit and capture of live crickets for consumption. While our preliminary work suggests individual mice display varying degrees of competence for cricket predation
(Fig. 1), with some adapting to predation demands faster than others, it is unknown how such innate behaviors are flexibly expressed during social competition or in relation to social rank.

• Patel RR, Patarino M, Kim K, Pamintuan R, Taschbach FH, Li H, Lee CR, van Hoek A, Castro R,
  Cazares C, Miranda RL, Jia C, Delahanty J, Batra K, Keyes L, Lobster A, Wichmann R, Benna M,
  Tye KM. (2026) Social isolation recruits amygdalamedial prefrontal cortex projections to escalate alcohol drinking in male mice. Nat Neurosci. https://doi.org/10.1038/s41593-026-02413-x
• Mills F, Lee CR, Howe JR, Li H, Keisler MN, Shao S, Taschbach FH, Lemieux ME, Aloboudi F, White
  J, Chan MG, Borio M, Keyes LR, Chen HS, Bushra F, Schneider GP, Lemmon DP, Lee KJ, Gross AL,
  Batra K, Patel RR, Asokan MM, Delahanty J, Cazares C, Heyman CR, Poll NB, Maree L, Wichmann
  R, Pereira TD, Benna MK, Root CM, Tye KM. (2026) Amygdalostriatal transition zone neurons encode sustained cue responses to guide defensive behaviors. Neuron. 2026 Sep 14:S0896-6273(26)00642-2. doi: 10.1016/j.neuron.2026.08.012. Epub ahead of print. PMID: 42735685.
  

Graduate Research with Dr. Christina Gremel

Daily life involves making adaptive decisions to achieve desired goals. Alcohol dependence is associated with decision-making dysfunctions that are thought to drive a relapsing cycle of intoxication, bingeing, withdrawal and craving that promotes excessive alcohol use despite negative consequences. The orbitofrontal cortex (OFC) has been widely implicated in value-based, goal-directed decision-making and has been shown to be dysfunctional in alcohol-dependence. The first part of my thesis, funded by the NSF-GRFP, aimed to investigate whether alcohol dependence-induced changes in OFC function altered OFC representation of action and outcome-related neural activity. To do so, we used a well-validated model of alcohol dependence, chronic intermittent ethanol (CIE), and performed in vivo extracellular recordings as mice performed an instrumental lever-pressing task in which they self-initiated lever-press responses and were required to hold down the lever past a minimum duration to earn a food reward. We found that 1) alcohol dependence disrupted goal-directed action control of task performance, 2) increased OFC activity associated with lever-pressing actions, and 3) decreased OFC activity during outcome-related epochs. Our results suggested that chronic alcohol exposure induced long-lasting disruptions to OFC function such that activity associated with actions was enhanced, but OFC activity contributions to outcome-related information was diminished. Overall our findings identified some of the complexity in how OFC’s contributions to decision-making computations are altered following alcohol exposure and further supported the OFC as a target brain region for the intervention of alcohol use disorder (AUD).

While our previous findings implicated OFC in representing actions during decision-making, it remained unknown how whether OFC populations support action-related computations, including computations important for inferring past action information. Given that OFC has been hypothesized as key for inference-based Pavlovian behavior, the second part of my thesis aimed to investigate whether OFC populations contributed to action-related inferences. To do so, we took advantage of our self-paced lever-press hold down task to probe how current and inferred prior lever press durations guide subsequent lever press performance. We found that 1) calcium activity of genetically identified OFC subpopulations differentially instantiated current and prior action information during ongoing decision-making, 2) transient optogenetic disruptions to OFC activity left mice unable to use recently executed durations to guide ongoing action performance, and that 3) a chronic functional loss of OFC circuit activity resulted in a compensatory mechanisms of repetitive action control, increasing behavioral reliance on the just completed action. Thus our results identified a novel role for OFC in the continuous integration of inferred action information in guiding adaptive behavior.

My thesis work thus far suggests OFC populations differentially contribute to actions during decision-making, and that such computations are disrupted in alcohol dependence. The final part of my thesis examined which OFC projections are important for behavioral control. OFC projects to secondary motor cortex (M2) and this circuit has been implicated in compulsive disorders and repetitive behaviors, including AUD. Thus far, we have found chronic alcohol exposure disrupts premotor circuits by altering cortico-cortical transfer of information about actions and their outcomes, thus providing mechanistic support for targeting activity of human premotor regions as a potential treatment in AUD.

• Schreiner D, Renteria R, Baltz ET, Cazares C, Gremel, CM (2022, in Review) Chronic alcohol exposure alters decision-making strategy via hyperactive premotor corticostriatal activity. Cell Reports.
• Cazares C, Schreiner DC, Valencia ML, Gremel CM. (2022) Orbitofrontal cortex populations are differentially recruited to support actions. Curr Biol. Nov 7;32(21):4675-4687.e5. doi: 10.1016/j.cub.2022.09.022. Epub 2022 Oct 3. PMID: 36195096; PMCID: PMC9643660.
• Schreiner D, Cazares C, Renteria R, Gremel, CM (2022) Information normally considered task-irrelevant drives decision-making and affects premotor circuit recruitment. Nat Commun. Apr 19;13(1):2134. doi: 10.1038/s41467-022-29807-2. PMID: 35440120; PMCID: PMC9018678.
• Yalcinbas, E. A., Cazares C., Gremel, C.M. (2021) Call For A More Balanced Approach to Understanding Orbital Frontal Cortex Function. Behavioral Neuroscience. 2021 Apr;135(2):255-266.
• Cazares C., Schreiner D., Gremel, C.M. (2021) Different Effects of Alcohol Exposure on Action and Outcome Related Orbitofrontal Cortex Activity. eNeuro. 2021 Mar PMID: 33785522.
• Renteria R., Cazares C., Baltz E.T., Schreiner D.C., Yalcinbas E.A., Stainkellner T., Hnasko T.S., Gremel, C.M. (2021) Mechanism for differential recruitment of orbitostriatal transmission during actions and outcomes following chronic alcohol exposure. Elife. 2021 Mar 17;10:e67065. doi: 10.7554/eLife.67065. PMID: 33729155.
• Renteria R., Cazares C., Gremel C.M. (2020) Habitual Ethanol Seeking and Licking Microstructure of Enhanced Ethanol Self-Administration in Ethanol-Dependent Mice. Alcohol Clin Exp Res. 2020 Feb 4. doi:10.1111/acer.14302.

• Ung H., Cazares C., Nanivadekar A., Kini, L. Wagenaar J., Becker D., Kahana M., Sperling M., Sharan A. Lucas T., Baltuch G., Litt B., Davis K.A. (2017) Interictal Epileptiform Activity outside the Seizure Onset Zone Impacts Cognition. Brain, Volume 140, Issue 8, 1 August 2017, 2157:2168

• Labruna, L., Tischler C., Cazares C., Greenhouse I., Duque J., Lebon F., Ivry RB. (2019) Planning face, hand, and leg movements: anatomical constraints on preparatory inhibition. J. Neurophysiol. 121, 1609:1620
• Duque J., Labruna L., Cazares C., Ivry R. (2014) Dissociating the influence of response selectionand task anticipation on corticospinal suppression during response preparation. Neuropsychologia 65:287:296
• Labruna L., Lebon F., Duque Julie., Klein P-A., Cazares C., Ivry R. (2014) Generic inhibition of the selected movement and constrained inhibition of non-selected movements during response preparation. Journal of Cognitive Neuroscience 26:2, 269:278