Memory engram, defined as physical changes elicited by learning, is consisted of sparse neuronal networks across the brain. Such changes mainly occur on synapses in the form of long-term potentiation (LTP). LTP is a persistent strengthening of synaptic ...

The goal of the current research was to investigate response selection and response execution when visual stimuli are consciously inaccessible. In order to display stimuli subliminally, stimuli were presented through metacontrast masking, a form of back...

Recognizing an object is usually faster and more accurate if that object has been encountered previously. Such experience-based priming of recognition can also be achieved through context-specific predictions about which objects are likely to appear together in a specific scene. Seeing a toaster, for instance, can facilitate subsequent recognition of contextually related objects such as a coffee-maker and a blender. The benefit of priming during recognition is typically associated with a physiological response reduction in occipito-temporal cortex. Moreover, the specific regions that exhibit response reduction in priming tasks can vary according to the nature of the relation between the target- and preceding prime-objects. Using event-related fMRI, we sought to elaborate the cortical mechanisms involved in experience-based facilitation of object recognition. Thus, we compared the different foci of response reductions for targets preceded by primes that were either the same object or were contextually relat...

Knowing how reward-associated cues influence instrumental behaviors is important for understanding many aspects of motivated behavior, including pathological states of motivation such as addiction. A prime example of this is the Pavlovian-to-instrumental transfer phenomenon (or PIT). In this procedure, after animals learn to associate a Pavlovian cue with reward (CS+) and, on separate occasions, learn to instrumentally respond for this reward, presentation of the CS+ during instrumental performance typically potentiates responding. Although little is known about the neurobiology of PIT, studies have clearly implicated glutamatergic (AMPA) and dopaminergic mechanisms. For instance, pretreatment with D1/D2-like (α-flupenthixol or Pimozide) antagonists was reported to disrupt PIT in rats (Dickinson et al, 2000). Here we further explore the role of dopamine receptor activation in PIT by pretreating C57/b6 mice, 10 min prior to PIT testing, with different IP doses of D1 or D2 receptor antagonists. We report tha...

Many women with epilepsy experience cycle-related increased seizure susceptibility, correlated with low progesterone levels, termed catamenial epilepsy. Recurring fluctuations in the levels of neurosteroids are prime candidates for mediating changes in neuronal excitability over the ovarian cycle, but the precise mechanisms responsible for their actions have yet to be elucidated. Progesterone metabolites are known to be potent modulators of GABAA receptors (GABAARs) and tonic inhibition mediated by δ subunit-containing GABAARs is an important site of action of neurosteroids. We have previously shown that changes in GABAARs δ subunit expression during the estrous cycle in mice accompany cyclic changes in seizure susceptibility and anxiety. The GABAR agonist THIP at low concentrations acts selectively at δ subunit-containing GABAARs to enhance the tonic GABAergic inhibition in dentate gyrus granules cells. When tested for its anticonvulsant activity in vivo against kainic acid-induced seizures, i.p. administ...

Neuronal activity induces a hierarchical program of mRNA transcription that involves both immediate early (IEG) and delayed early genes (DERG) that are hypothesized to underlie learning-dependent neuronal plasticity (Lanahan & Worley, 1998). IEGs are transcribed within minutes of a novel learning experience, as can be visualized by the technique known as cellular compartment analysis of temporal activity by fluorescence in situ hybridization (catFISH). Despite the wealth of data generated on IEG expression, relatively little is known about DERGs. This class of genes shows stimulus-dependent transcriptional induction similar to IEGs; however, an initial wave of transcription and de novo protein synthesis is necessary in order for the DERGs to be transcribed (Goelet et al., 1986). DERGs are implicated in mediating long-term changes in cell function in many non-neuronal systems. Thus, these gene products are a prime candidate for mediating long-term functional changes associated with learning and memory. Desp...

Modulation of voltage-gated Ca2+ channels via G-protein-coupled receptors is a prime mechanism regulating neurotransmitter release and synaptic plasticity. Despite extensive studies, the molecular mechanism underlying Gq/11-mediated modulation remains unclear. We found cloned and native N-type Ca2+ channels to be regulated by phosphotidylinositol 4,5-bisphosphate (PIP2). In inside-out oocyte patches, PIP2 greatly attenuated or reversed the observed rundown of expressed channels. In sympathetic neurons, muscarinic M1 ACh receptor suppression of the Ca2+ current ( I Ca) was temporally correlated with PIP2 hydrolysis, blunted by PIP2 in whole-cell pipettes, attenuated by expression of PIP2-sequestering proteins, and became irreversible when PIP2 synthesis was blocked. We also probed mechanisms of receptor specificity. Although bradykinin also induced PIP2 hydrolysis, it did not inhibit I Ca. However, bradykinin receptors became nearly as effective as M1 receptors when PIP2 synthesis, IP3 receptors, or the act...

Coordinated activity of rhythm generating neural networks is a key requirement for fine-tuned motor behavior. Synchronization of large oscillatory networks has been also suggested as a way of binding perceptual properties. The lobster stomatogastric ganglion (STG) has been one of the prime experimental models of interactions in oscillatory neural networks. Here, central pattern generators (CPGs) such as the pyloric and gastric mill networks each having different synaptic connectivity and frequencies produce a wide variety of neural interactions. The topological and biophysical constraints for coordinated activity between identical CPGs has been less investigated and less understood. In our present study we address this problem by using two intact pyloric networks from two different STG preparations. Although pyloric networks of different STGs naturally generate the same motor pattern, their endogenous frequencies and the phase-relationships of their component neurons are different. Hence, coordination of t...

In the postnatal subventricular zone (SVZ) glial fibrillary acidic protein (GFAP)-immunopositive cells (called here astrocyte-like cells) are thought to be stem cells and closely encapsulate neuronal precursors. SVZ astrocyte-like cells are thus in a prime location to receive signals from neuronal precursors. As GABA and GABA synthetic enzyme are present in SVZ precursors, we examined whether GABA acts as a signaling molecule between SVZ cells using immunostaining and patch-clamp recordings in acute brain slices from transgenic mice expressing GFP on the promoter of GFAP. We found that astrocyte-like cells express functional GABAA receptors that are nonsynaptically activated following depolarization of SVZ precursors by either electrical stimulation or 5 mM-increase in extracellular K+. GABAA receptors were also tonically activated in 60% of recorded astrocyte-like cells. Furthermore, neuronal precursors contained GABA and displayed spontaneous depolarizations of similar amplitudes than those induced by K+...

The molecular mechanisms controlling the oscillatory synthesis of melatonin in rat pineal gland involve the rhythmic expression of several genes including arylalkylamine N -acetyltransferase ( AA-NAT ), inducible cAMP early repressor ( ICER ), and Fos-related antigen-2 ( fra-2 ). Here we show that the calcium sensors downstream regulatory element antagonist modulator/potassium channel interacting protein (DREAM/KChIP)-3 and KChIP-1, -2 and -4 bind to downstream regulatory element (DRE) sites located in the regulatory regions of these genes and repress basal and induced transcription from ICER, fra-2 or AA-NAT promoters. Importantly, we demonstrate that the endogenous binding activity to DRE sites shows day-night oscillations in rat pineal gland and retina but not in the cerebellum. The peak of DRE binding activity occurs during the day period of the circadian cycle, coinciding with the lowest levels of fra-2, ICER , and AA-NAT transcripts. We show that a rapid clearance of DRE binding activity during the e...