Parkinson's disease (PD) is characterized by progressive dopamine (DA) neuron loss in the SNc. In contrast, DA neurons in the VTA are relatively protected from neurodegeneration, but the underlying mechanisms for this resilience remain poorly understood. Recent work suggests that expression of the vesicular glutamate transporter 2 (VGLUT2) selectively impacts midbrain DA neuron vulnerability. We investigated whether altered DA neuron VGLUT2 expression determines neuronal resilience in rats exposed to rotenone, a mitochondrial complex I inhibitor and toxicant model of PD. We discovered that VTA/SNc DA neurons that expressed VGLUT2 are more resilient to rotenone-induced DA neurodegeneration. Surprisingly, the density of neurons with detectable VGLUT2 expression in the VTA and SNc increases in response to rotenone. Furthermore, dopaminergic terminals within the NAc, where the majority of VGLUT2-expressing DA neurons project, exhibit greater resilience compared with DA terminals in the caudate/putamen. More br...

Different species of animals can discriminate numerosity, the countable number of objects in a set. The representations of countable numerosities have been deciphered down to the level of single neurons. However, despite its importance for human number theory, a special numerical quantity, the empty set (numerosity zero), has remained largely unexplored. We explored the behavioral and neuronal representation of the empty set in carrion crows. Crows were trained to discriminate small numerosities including the empty set. Performance data showed a numerical distance effect for the empty set in one crow, suggesting that the empty set and countable numerosities are represented along the crows' “mental number line.” Single-cell recordings in the endbrain region nidopallium caudolaterale (NCL) showed a considerable proportion of NCL neurons tuned to the preferred numerosity zero. As evidenced by neuronal distance and size effects, NCL neurons integrated the empty set in the neural number line. A subsequent neuro...

José Antonio Noriega-Prieto, Laura Eva Maglio, Jonathan A. Zegarra-Valdivia, Jaime Pignatelli, Ana M. Fernandez, et al. (see pages [4768–4781][1]) Insulin-like growth factor 1 (IGF-1) is a peptide with diverse roles in the CNS, including promotion of neurogenesis, dendrite growth, and synaptic

Insulin-like growth factor-I (IGF-I) signaling plays a key role in learning and memory processes. While the effects of IGF-I on neurons have been studied extensively, the involvement of astrocytes in IGF-I signaling and the consequences on synaptic plasticity and animal behavior remain unknown. We have found that IGF-I induces long-term potentiation (LTPIGFI) of the postsynaptic potentials that is caused by a long-term depression of inhibitory synaptic transmission in mice. We have demonstrated that this long-lasting decrease in the inhibitory synaptic transmission is evoked by astrocytic activation through its IGF-I receptors (IGF-IRs). We show that LTPIGFI not only increases the output of pyramidal neurons, but also favors the NMDAR-dependent LTP, resulting in the crucial information processing at the barrel cortex since specific deletion of IGF-IR in cortical astrocytes impairs the whisker discrimination task. Our work reveals a novel mechanism and functional consequences of IGF-I signaling on cortical ...

Our daily lives consist of many repeated events. This poses a challenge for the memory system: because our experiences may contain related elements, we often have to distinguish between similar memories ([O'Reilly and McClelland, 1994][1]). The brain can help mitigate interference between memories

Taste neurons are functionally and molecularly diverse, but their morphologic diversity remains completely unexplored. Using sparse cell genetic labeling, we provide the first reconstructions of peripheral taste neurons. The branching characteristics across 96 taste neurons show surprising diversity in their complexities. Individual neurons had 1–17 separate arbors entering between one and seven taste buds, 18 of these neurons also innervated non-taste epithelia. Axon branching characteristics are similar in gustatory neurons from male and female mice. Cluster analysis separated the neurons into four groups according to branch complexity. The primary difference between clusters was the amount of the nerve fiber within the taste bud available to contact taste-transducing cells. Consistently, we found that the maximum number of taste-transducing cells capable of providing convergent input onto individual gustatory neurons varied with a range of 1–22 taste-transducing cells. Differences in branching character...

Repeated cocaine exposure causes dendritic spine loss in the orbitofrontal cortex, which might contribute to poor orbitofrontal cortical function following drug exposure. One challenge, however, has been verifying links between neuronal structural plasticity and behavior, if any. Here we report that cocaine self-administration triggers the loss of dendritic spines on excitatory neurons in the orbitofrontal cortex of male and female mice (as has been reported in rats). To understand functional consequences, we locally ablated neuronal β1-integrins, cell adhesion receptors that adhere cells to the extracellular matrix and thus support dendritic spine stability. Degradation of β1-integrin tone: 1) caused dendritic spine loss; 2) exaggerated cocaine-seeking responses in a cue-induced reinstatement test; and 3) impaired the ability of mice to integrate new learning into familiar routines – a key function of the orbitofrontal cortex. Stimulating Abl-related gene (Arg) kinase, over-expressing Proline-rich tyrosin...

The orbitofrontal cortex (OFC) is a brain region involved in higher-order decision-making. Rodent studies show that cocaine self-administration (CSA) reduces OFC contribution to goal-directed behavior and behavioral strategies to avoid drug intake. This change in OFC function persists for many weeks after cocaine withdrawal, suggesting involvement in the process of addiction. The mechanisms underlying impaired OFC function by cocaine are not well-understood. However, studies implicate altered OFC serotonin (5-HT) function in disrupted cognitive processes during addiction and other psychiatric disorders. Thus, it is hypothesized that cocaine impairment of OFC function involves changes in 5-HT signaling, and previous work shows that 5-HT1A and 5-HT2A receptor-mediated effects on OFC pyramidal neurons (PyNs) are impaired weeks after cocaine withdrawal. However, 5-HT effects on other contributors to OFC circuit function have not been fully investigated, including the parvalbumin-containing, fast-spiking intern...

Oscillation-based models of speech perception postulate a cortical computational principle by which decoding is performed within a window structure derived by a segmentation process. Segmentation of syllable-size chunks is realized by a theta oscillator. We provide evidence for an analogous role of a delta oscillator in the segmentation of phrase-sized chunks. We recorded Magnetoencephalography (MEG) in humans, while participants performed a target identification task. Random-digit strings, with phrase-long chunks of two digits, were presented at chunk rates of 1.8 Hz or 2.6 Hz, inside or outside the delta frequency band (defined here to be 0.5 - 2 Hz). Strong periodicities were elicited by chunk rates inside of delta in superior, middle temporal areas and speech-motor integration areas. Periodicities were diminished or absent for chunk rates outside delta, in line with behavioral performance. Our findings show that prosodic chunking of phrase-sized acoustic segments is correlated with acoustic-driven delt...

Identifying true motivation for Pareto lies, which are mutually beneficial for both the liar and others, can be challenging because different covert motivations can lead to identical overt behavior. In this study, we adopted a brain-fingerprinting approach, combining both univariate and multivariate analyses to estimate individual measures of selfish motivation in Pareto lies by the degree of multivoxel neural representation in the medial prefrontal cortex (MPFC) for Pareto lies conforms with those for selfish vs. altruistic lies in human participants of either sex. An increase in selfish motivation for Pareto lies was associated with higher mean-level activity in both ventral and rostral MPFC. The former showed an increased pattern similarity to selfish lies and the latter showed a decreased pattern similarity to altruistic lies. Higher ventral MPFC pattern similarity predicted faster response time in Pareto lies. Our findings demonstrated that hidden selfish motivation in white lies can be revealed by ne...