The Russian farm-fox experiment is an unusually long-running and well-controlled study designed to replicate wolf-to-dog domestication. As such, it offers an unprecedented window onto the neural mechanisms governing the evolution of behavior. Here we report evolved changes to gray matter morphology resulting from selection for tameness versus aggressive responses toward humans in a sample of 30 male fox brains. Contrasting with standing ideas on the effects of domestication on brain size, tame foxes did not show reduced brain volume. Rather, gray matter volume in both the tame and aggressive strains was increased relative to conventional farm foxes bred without deliberate selection on behavior. Furthermore, tame- and aggressive-enlarged regions overlapped substantially, including portions of motor, somatosensory, and prefrontal cortex, amygdala, hippocampus, and cerebellum. We also observed differential morphologic covariation across distributed gray matter networks. In one prefrontal-cerebellum network, t...

William N. Grimes, Didem Göz Aytürk, Mrinalini Hoon, Takeshi Yoshimatsu, Clare Gamlin, et al. (see pages [6018–6037][1]) The retina is a complex structure with an astounding number of cell types. For example, an inventory based on electron micrograph reconstructions (Helmstaedter et al., 2013

Neuropeptide secretion from dense-core vesicles (DCVs) controls many brain functions. Several components of the DCV exocytosis machinery have recently been identified, but the participation of a SEC1/MUNC18 (SM) protein has remained elusive. Here, we tested the ability of the three exocytic SM proteins expressed in the mammalian brain, MUNC18-1/2/3, to support neuropeptide secretion. We quantified DCV exocytosis at a single vesicle resolution on action potential (AP) train-stimulation in mouse CNS neurons (of unknown sex) using pHluorin-tagged and/or mCherry-tagged neuropeptide Y (NPY) or brain-derived neurotrophic factor (BDNF). Conditional inactivation of Munc18-1 abolished all DCV exocytosis. Expression of MUNC18-1, but not MUNC18-2 or MUNC18-3, supported DCV exocytosis in Munc18-1 null neurons. Heterozygous (HZ) inactivation of Munc18-1 , as a model for reduced MUNC18-1 expression, impaired DCV exocytosis, especially during the initial phase of train-stimulation, when the release was maximal. These dat...

Although the anterior temporal lobe (ATL) comprises several anatomic and functional subdivisions, it is often reduced to a homogeneous theoretical entity, such as a domain-general convergence zone, or “hub,” for semantic information. Methodological limitations are largely to blame for the imprecise mapping of function to structure in the ATL. There are two major obstacles to using fMRI to identify the precise functional organization of the ATL: the difficult choice of stimuli and tasks to activate, and dissociate, specific regions within the ATL; and poor signal quality because of magnetic field distortions near the sinuses. To circumvent these difficulties, we developed a data-driven parcellation routine using resting-state fMRI data (24 females, 64 males) acquired using a sequence that was optimized to enhance signal in the ATL. Focusing on patterns of functional connectivity between each ATL voxel and the rest of the brain, we found that the ATL comprises at least 34 distinct functional parcels that are...

The lateral (LA) and basolateral (BL) nuclei of the amygdala regulate emotional behaviors. Despite their dissimilar extrinsic connectivity, they are often combined, perhaps because their cellular composition is similar to that of the cerebral cortex, including excitatory principal cells reciprocally connected with fast-spiking interneurons (FSIs). In the cortex, this microcircuitry produces gamma oscillations that support information processing and behavior. We tested whether this was similarly the case in the rat (males) LA and BL using extracellular recordings, biophysical modeling, and behavioral conditioning. During periods of environmental assessment, both nuclei exhibited gamma oscillations that stopped upon initiation of active behaviors. Yet, BL exhibited more robust spontaneous gamma oscillations than LA. The greater propensity of BL to generate gamma resulted from several microcircuit differences, especially the proportion of FSIs and their interconnections with principal cells. Furthermore, gamm...

Visual word recognition, at a minimum, involves the processing of word form and lexical information. Opinions diverge on the spatiotemporal distribution of and interaction between the two types of information. Feedforward theory argues that they are processed sequentially, whereas interactive theory advocates that lexical information is processed fast and modulates early word form processing. To distinguish between the two theories, we applied stereoelectroencephalography (SEEG) to 33 human adults with epilepsy (25 males and eight females) during visual lexical decisions. The stimuli included real words (RWs), pseudowords (PWs) with legal radical positions, nonwords (NWs) with illegal radical positions, and stroked-changed words (SWs) in Chinese. Word form and lexical processing were measured by the word form effect (PW versus NW) and lexical effect (RW versus PW), respectively. Gamma-band (60 ∼ 140 Hz) SEEG activity was treated as an electrophysiological measure. A word form effect was found in eight left...

Vocal learning species must form and extensively hone associations between sounds and social contingencies. In songbirds, dopamine signaling guides song motor production, variability, and motivation, but it is unclear how dopamine regulates fundamental auditory associations for learning new sounds. We hypothesized that dopamine regulates learning in the auditory pallium, in part by interacting with local neuroestradiol signaling. Here, we show that zebra finch auditory neurons frequently coexpress D1 receptor (D1R) protein, neuroestradiol-synthase, GABA, and parvalbumin (PV). Auditory classical conditioning increased neuroplasticity gene induction in D1R-positive neurons. In vitro , D1R pharmacological activation reduced the amplitude of GABAergic and glutamatergic currents and increased the latter's frequency. In vivo , D1R activation reduced the firing of putative interneurons, increased the firing of putative excitatory neurons, and made both neuronal types unable to adapt to novel stimuli. Together, th...

Amacrine cells are interneurons composing the most diverse cell class in the mammalian retina. They help encode visual features, such as edges or directed motion, by mediating excitatory and inhibitory interactions between input (i.e., bipolar) and output (i.e., ganglion) neurons in the inner plexiform layer (IPL). Like other brain regions, the retina also contains glial cells that contribute to neurotransmitter uptake, metabolic regulation, and neurovascular control. Here, we report that, in mouse retina (of either sex), an abundant, though previously unstudied inhibitory amacrine cell is coupled directly to Müller glia. Electron microscopic reconstructions of this amacrine type revealed chemical synapses with known retinal cell types and extensive associations with Müller glia, the processes of which often completely ensheathe the neurites of this amacrine cell. Microinjecting small tracer molecules into the somas of these amacrine cells led to selective labeling of nearby Müller glia, leading us to sugg...

Approximately 5 million people die from diseases related to nicotine addiction and tobacco use each year. The nicotine-induced increase of corticomesolimbic dopaminergic (DAergic) transmission and hypodopaminergic conditions occurring during abstinence are important for maintaining drug-use habits. We examined the notion of reequilibrating DAergic transmission by inhibiting phosphodiesterase 7 (PDE7), an intracellular enzyme highly expressed in the corticomesolimbic circuitry and responsible for the degradation of cyclic adenosine monophosphate (cAMP), the main second messenger modulated by DA receptor activation. Using selective PDE7 inhibitors, we demonstrated in male rats that systemic PDE7 enzyme inhibition reduced nicotine self-administration and prevented reinstatement to nicotine seeking evoked by cues or by the pharmacological stressor yohimbine. The effect was also observed by direct application of the PDE7 inhibitors into the nucleus accumbens (NAc) shell but not into the core. Inhibition of PDE7...