Recent findings have shifted the view of cholecystokinin (CCK) from being a cellular neuronal marker to being recognized as a crucial neuropeptide pivotal in synaptic plasticity and memory processes. Despite its now appreciated importance in various brain regions and abundance in the basal ganglia, its role in the striatum, which is vital for motor control, remains unclear. This study sought to fill this gap by performing a comprehensive investigation of the role of CCK in modulating striatal medium spiny neuron (MSN) membrane properties, as well as the secondary somatosensory cortex S2 to MSN synaptic transmission and plasticity in rodents. Using in vivo optopatch-clamp recording in mice on identified MSNs, we showed that the application of CCK receptor Type 2 (CCK2R) antagonists decreases corticostriatal transmission in both direct and indirect pathway MSNs. Moving to an ex vivo rat preparation to maximize experimental access, we showed that CCK2R inhibition impacts MSN membrane properties by reducing sp...

Orbitofrontal cortex (OFC) damage elicits impulsivity and perseveration, and impairments in OFC function may underlie compulsive drug seeking in cocaine users. To test this hypothesis, we assessed the effects of fiber-sparing lesions or functional inactivation of OFC subregions on cocaine seeking in rats. Rats were trained to lever press for intravenous cocaine (0.20 mg/infusion) paired with the presentations of light plus tone stimuli. Responding was then allowed to extinguish. Rats received bilateral NMDA (0.1 M) or sham lesions of the lateral OFC (lOFC) or medial OFC (mOFC) before self-administration training (experiment 1) or muscimol plus baclofen (0.1 and 1.0 mM) or vehicle infusions into the lOFC or mOFC before reinstatement testing (experiment 2). The effects of these manipulations on reinstatement of cocaine seeking (i.e., responding on the previously cocaine-paired lever) were assessed in the presence of the light plus tone stimuli or after a cocaine priming injection (10 mg/kg, i.p.). Post-train...

To investigate neural substrate of semantic contextual effects on word processing, MEGs were recorded by related and unrelated prime-target pairs during a categorical decision task. The pair stimuli, which consisted of Japanese katakana (syllabogram) nouns, were arranged into four conditions (category matching x semantically related). All stimuli were presented for 100 ms in the left visual field. After the presentation of prime, a target was presented followed by an inter-stimulus interval of 1000 ms, and then a cue for pressing button was presented at 2000 ms. Subjects were instructed to decide immediately whether the target was in the category or not, and to respond after the cue. A 148-channel whole-head system was used for the MEG measurement, and cortical current distributions were calculated using the minimum norm least square approach and a realistic brain model. The current distribution showed that large activation occurred in the occipital visual areas along the ventral visual processing stream i...

Studies of unconscious priming have shown that even if the presentation of a prime is not accompanied by conscious awareness it can alter responses to a subsequently present target stimuli. This remains true even if the only relationship between prime and target is of a semantic nature. This has been taken as evidence of highly abstract information extraction during unconscious word perception. A new approach to investigating the level of information extracted from unperceived stimuli was employed to search for evidence that word meaning is extracted from masked stimuli. The traditional approach is to present masked stimuli below the level of reported perception and measure the influence on an indirect task, such a subsequent lexical decision performance. The present technique employs electroencephalography to directly contrast the evoked response of two classes of stimuli both presented below the level of conscious perception. Using this technique, not only demonstrated that the brain differentiates betwe...

In the lobster, presynaptic inhibition of odor signals is mediated by ionotropic GABA and histamine receptors (Wachoviak et al , Microsc. Res. Tech. 58:365-375, 2002). We previously isolated a cDNA clone encoding an ionotropic glutamate receptor subunit (Lobster GluR1) using representational difference analysis of the lobster olfactory organ. Here, we report the isolation of a cDNA encoding a second glutamate receptor subunit that is also expressed in the lobster olfactory organ. Lobster olfactory organ cDNA was used to generate a plasmid library containing 120 bp inserts that were generated by PCR using degenerate primers. Selected inserts were sequenced and tested for homology using blast analysis at the NCBI web site. 5 prime and 3 prime RACE reactions were performed on one positive insert to generate the full-length clone. Expression of the clone was tested by PCR on cDNA from several lobster tissues. In situ hybridization was performed on lobster olfactory organ using 50 micron vibratome slices and di...

The annual Society for Neuroscience (SfN) meeting is a bonanza of scientific achievement: famous keynote speakers, beautiful scientific results, and award ceremonies. This focus is exciting and invigorating but glosses over the many failures, mistakes, and rejections that typically lead to scientific success. Our goal has been to create a space within the annual SfN meeting for open conversation about scientific failure and, by doing so, increase transparency, resilience, and mental well-being within our community. In this article, we share the materials that we have used at SfN during the past 4 years (2021–2024) to promote discussions of scientific failure, including formal storytelling, individual and interactive games, and confessionals. For each activity, we provide the rationale and practical guidance regarding logistics and usage. We hope this will aid scientists interested in adapting the activities for their own communities or local events. We end with a call for scientific institutions to commit ...

Neuroligins (NLGNs) are a family of postsynaptic adhesion molecules that bind to their presynaptic partners, neurexins, facilitating the formation and maintenance of synapses. In humans, there are five genes encoding NLGNs ( NLGN1-3 , NLGN4X , and NLGN4Y ), with NLGN1-3 having highly conserved counterparts in rodents, allowing these genes to be studied with high confidence of translational validity in mouse models. Human NLGN4X and 4Y were often assumed to serve similar functions because they share a 97% sequence homology, whereas mouse NLGN4-like is quite divergent. Many NLGN-mediated synaptic effects are modulated through post-translation modifications, which exert temporal and spatial control. In this report, we characterize a conserved phosphorylation site, serine 712, on NLGN4X and 4Y. Despite serine 712 being located in a highly conserved region between NLGN4X and 4Y, we observed kinase specificity. PKA exclusively phosphorylates NLGN4X S712, whereas Cdk5 phosphorylates S712 on both NLGN4X and 4Y. NL...

Neurons adapt to chronic activity changes by modifying synaptic properties, including neurotransmitter release. However, whether neuropeptide release via dense core vesicles (DCVs)—a distinct regulated secretory pathway—undergoes similar adaptation remains unclear. Here, we demonstrate that 24 h action potential blockade leads to significant DCV accumulation in primary mouse cortical neurons of both sexes. Reactivation with action potential trains induced enhanced Ca2+ influx and 700% more DCV exocytosis compared with control neurons. Notably, total DCV cargo protein levels were unchanged, while mRNA levels of corresponding genes were reduced. Blocking neurotransmitter release with Tetanus toxin induced DCV accumulation, similar to that induced by network silencing with TTX. Hence, chronic network silencing triggers increased DCV accumulation due to reduced exocytosis during silencing. These accumulated DCVs can be released upon reactivation resulting in a massive potentiation of DCV exocytosis, possibly c...

Brain-derived estrogen (17β-estradiol, E2) is a neuromodulator that plays important roles in neural plasticity and network excitability. Chronic inhibition of estrogen synthesis is used in adjuvant breast cancer therapy for estrogen receptor-positive tumors and may have been associated with cognitive and affective side effects. Here, we have developed a model of adjuvant therapy in female ovariectomized mice in which the E2 biosynthetic enzyme aromatase is inhibited by letrozole (1 mg/kg/day, i.p., for up to 3 weeks), Using two-photon longitudinal in vivo imaging in Thy1-GFP-M mice, we found that spine density in the apical dendrites of neocortical layer 5 pyramidal cells was unaffected by letrozole treatment but spine turnover was reduced. LTP in layer 4 to layer 2/3 synapses in the somatosensory cortex was also reduced in slices from letrozole-treated mice, showing deficits in structural and functional plasticity resulting from aromatase inhibition. Ovariectomized mice performed worse than intact control...

The effects of cutaneous stimulation on muscle activation range from enhancement to inhibition. Layne et al.,(2000) have shown that stimulation to the sole increases muscle activation in microgravity and 1g. The purpose of this investigation was to determine if stimulation to the sole similarly modified muscle activation when muscles were functioning in a postural or voluntary role. A second goal was to investigate if increasing levels of stimulation modified the magnitude of muscle activation. The TA was monitored using surface EMG during ankle dorsiflexion to investigate activation when a muscle was serving as the prime mover. Several lower limb muscles were monitored during rapid arm raises to investigate neuromuscular responses of muscles traditionally serving bipedal postural control functions. Both movements were completed in supine with four levels of pressure (0, 8, 16 and 24 psi) applied to the sole between 100 and 50 ms prior to the onset of the prime mover. The rapid arm raise was also completed...