scholarly journals Region specific knockdown of Parvalbumin or Somatostatin produces neuronal and behavioral deficits consistent with those observed in schizophrenia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stephanie M. Perez ◽  
Angela Boley ◽  
Daniel J. Lodge
Keyword(s):  
Prefrontal Cortex ◽  
Neuronal Activity ◽  
Negative Symptoms ◽  
Cell Activity ◽  
Dopamine Neuron ◽  
Neuron Activity ◽  
Behavioral Deficits ◽  
Mesolimbic Dopamine System ◽  
Downstream Effects ◽  
And Behavior

Abstract The anterior hippocampus and prefrontal cortex are regions linked to symptoms of schizophrenia. The anterior hippocampus is believed to be a key regulator of the mesolimbic dopamine system and is thought to be the driving force contributing to positive symptoms, while the prefrontal cortex is involved in cognitive flexibility and negative symptoms. Aberrant activity in these regions is associated with decreases in GABAergic markers, indicative of an interneuron dysfunction. Specifically, selective decreases are observed in interneurons that contain parvalbumin (PV) or somatostatin (SST). Here, we used viral knockdown in rodents to recapitulate this finding and examine the region-specific roles of PV and SST on neuronal activity and behaviors associated with positive, negative and cognitive symptoms. We found that PV and SST had differential effects on neuronal activity and behavior when knocked down in the ventral hippocampus (vHipp) or medial prefrontal cortex (mPFC). Specifically, SST or PV knockdown in the vHipp increased pyramidal cell activity of the region and produced downstream effects on dopamine neuron activity in the ventral tegmental area (VTA). In contrast, mPFC knockdown did not affect the activity of VTA dopamine neuron activity; however, it did produce deficits in negative (social interaction) and cognitive (reversal learning) domains. Taken together, decreases in PV and/or SST were sufficient to produce schizophrenia-like deficits that were dependent on the region targeted.

scholarly journals Biomolecular Aspects of Schizophrenia

2019 ◽  
Vol 3 (2) ◽  
pp. 38-43
Author(s):  
Patricia Wulandari
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prefrontal Cortex ◽  
Negative Symptoms ◽  
Neuronal Cell ◽  
Dsm V ◽  
Schizophrenic Patients ◽  
The Central Nervous System ◽  
And Behavior ◽  
Positive And Negative Symptoms

Abstract Schizophrenia is a common psychiatric disorder, which is characterized by severe distortion of reality; disturbances in thoughts, feelings and behavior; according to DSM V is a disorder form deviations fundamentals and characteristics of thought and perception, and by the innapropriate or blunted affect. The influence of genetics is believed to have a role in psychiatric disorders, especially if the disorder has occurred in young adults or adolescents. The pathophysiology of schizophrenia is closely related to disorders of the biomolecular aspects of the central nervous system. Dopamine activity in the striatal area and prefrontal cortex is a mechanism believed to be the cause of the emergence of positive and negative symptoms in schizophrenia. Meanwhile, neuronal cell apoptosis and increased oxidants, especially in the basal ganglia and prefrontal cortex areas cause worsening of negative symptoms experienced by schizophrenic patients.

scholarly journals Orexin receptor antagonists reverse aberrant dopamine neuron activity and related behaviors in a rodent model of stress-induced psychosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hannah B. Elam ◽  
Stephanie M. Perez ◽  
Jennifer J. Donegan ◽  
Daniel J. Lodge
Keyword(s):  
United States ◽  
Sensorimotor Gating ◽  
The United States ◽  
Dopamine Neuron ◽  
Neuron Activity ◽  
Sprague Dawley ◽  
Post Traumatic Stress ◽  
Neuron Population ◽  
Population Activity ◽  
Novel Approach

AbstractPost-traumatic stress disorder (PTSD) is a prevalent condition affecting approximately 8% of the United States population and 20% of United States combat veterans. In addition to core symptoms of the disorder, up to 64% of individuals diagnosed with PTSD experience comorbid psychosis. Previous research has demonstrated a positive correlation between symptoms of psychosis and increases in dopamine transmission. We have recently demonstrated projections from the paraventricular nucleus of the thalamus (PVT) to the nucleus accumbens (NAc) can regulate dopamine neuron activity in the ventral tegmental area (VTA). Specifically, inactivation of the PVT leads to a reversal of aberrant dopamine system function and psychosis-like behavior. The PVT receives dense innervation from orexin containing neurons, therefore, targeting orexin receptors may be a novel approach to restore dopamine neuron activity and alleviate PTSD-associated psychosis. In this study, we induced stress-related pathophysiology in male Sprague Dawley rats using an inescapable foot-shock procedure. We observed a significant increase in VTA dopamine neuron population activity, deficits in sensorimotor gating, and hyperresponsivity to psychomotor stimulants. Administration of selective orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) antagonists (SB334867 and EMPA, respectively) or the FDA-approved, dual-orexin receptor antagonist, Suvorexant, were found to reverse stress-induced increases in dopamine neuron population activity. However, only Suvorexant and SB334867 were able to reverse deficits in behavioral corelates of psychosis. These results suggest that the orexin system may be a novel pharmacological target for the treatment of comorbid psychosis related to PTSD.

scholarly journals Histamine H1 receptor deletion in cholinergic neurons induces sensorimotor gating ability deficit and social impairments in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Li Cheng ◽  
Cenglin Xu ◽  
Lu Wang ◽  
Dadao An ◽  
Lei Jiang ◽  
...  
Keyword(s):  
Functional Outcomes ◽  
Negative Symptoms ◽  
Cholinergic Neurons ◽  
Sensorimotor Gating ◽  
Social Impairment ◽  
H1 Receptor ◽  
Behavioral Deficits ◽  
Social Impairments ◽  
Cholinergic Projections ◽  
Functional Deficiency

AbstractNegative symptoms in schizophrenia strongly contribute to poor functional outcomes, however its pathogenesis is still unclear. Here, we found that histamine H1 receptor (H1R) expression in basal forebrain (BF) cholinergic neurons was decreased in patients with schizophrenia having negative symptoms. Deletion of H1R gene in cholinergic neurons in mice resulted in functional deficiency of cholinergic projections from the BF to the prefrontal cortex and in the formation of sensorimotor gating deficit, social impairment and anhedonia-like behavior. These behavioral deficits can be rescued by re-expressing H1R or by chemogenetic activation of cholinergic neurons in the BF. Direct chemogenetic inhibition of BF cholinergic neurons produced such behavioral deficits and also increased the susceptibility to hyperlocomotion. Our results suggest that the H1R deficiency in BF cholinergic neurons is critical for sensorimotor gating deficit, social impairments and anhedonia-like behavior. This finding may help to understand the genetic and biochemical bases of negative symptoms in schizophrenia.

scholarly journals Changes in Prefrontal Cortex–Thalamic Circuitry after Acoustic Trauma

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 77
Author(s):  
Kristin M. Barry ◽  
Donald Robertson ◽  
Wilhelmina H. A. M. Mulders
Keyword(s):  
Electrical Stimulation ◽  
Prefrontal Cortex ◽  
Auditory System ◽  
Acoustic Trauma ◽  
Neuron Activity ◽  
Compensatory Mechanism ◽  
Efferent Connections ◽  
Medial Geniculate ◽  
Central Auditory Pathways ◽  
Stimulation Of

In the adult auditory system, loss of input resulting from peripheral deafferentation is well known to lead to plasticity in the central nervous system, manifested as reorganization of cortical maps and altered activity throughout the central auditory pathways. The auditory system also has strong afferent and efferent connections with cortico-limbic circuitry including the prefrontal cortex and the question arises whether this circuitry is also affected by loss of peripheral input. Recent studies in our laboratory showed that PFC activation can modulate activity of the auditory thalamus or medial geniculate nucleus (MGN) in normal hearing rats. In addition, we have shown in rats that cochlear trauma resulted in altered spontaneous burst firing in MGN. However, whether the PFC influence on MGN is changed after cochlear trauma is unknown. We investigated the effects of electrical stimulation of PFC on single neuron activity in the MGN in anaesthetized Wistar rats 2 weeks after acoustic trauma or sham surgery. Electrical stimulation of PFC showed a variety of effects in MGN neurons both in sham and acoustic trauma groups but inhibitory responses were significantly larger in the acoustic trauma animals. These results suggest an alteration in functional connectivity between PFC and MGN after cochlear trauma. This change may be a compensatory mechanism increasing sensory gating after the development of altered spontaneous activity in MGN, to prevent altered activity reaching the cortex and conscious perception.

Rule-dependent neuronal activity in the prefrontal cortex

1999 ◽  
Vol 126 (3) ◽  
pp. 315-335 ◽  
Author(s):  
Ilsun M. White ◽  
S. P. Wise
Keyword(s):  
Prefrontal Cortex ◽  
Neuronal Activity

scholarly journals Dissociable roles of cortical excitation-inhibition balance during patch-leaving versus value-guided decisions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Luca F. Kaiser ◽  
Theo O. J. Gruendler ◽  
Oliver Speck ◽  
Lennart Luettgau ◽  
Gerhard Jocham
Keyword(s):  
Decision Making ◽  
Prefrontal Cortex ◽  
Neuronal Activity ◽  
Ventromedial Prefrontal Cortex ◽  
Anterior Cingulate ◽  
Mutual Inhibition ◽  
Dorsal Anterior Cingulate Cortex ◽  
Cortical Excitation ◽  
The Cost

AbstractIn a dynamic world, it is essential to decide when to leave an exploited resource. Such patch-leaving decisions involve balancing the cost of moving against the gain expected from the alternative patch. This contrasts with value-guided decisions that typically involve maximizing reward by selecting the current best option. Patterns of neuronal activity pertaining to patch-leaving decisions have been reported in dorsal anterior cingulate cortex (dACC), whereas competition via mutual inhibition in ventromedial prefrontal cortex (vmPFC) is thought to underlie value-guided choice. Here, we show that the balance between cortical excitation and inhibition (E/I balance), measured by the ratio of GABA and glutamate concentrations, plays a dissociable role for the two kinds of decisions. Patch-leaving decision behaviour relates to E/I balance in dACC. In contrast, value-guided decision-making relates to E/I balance in vmPFC. These results support mechanistic accounts of value-guided choice and provide evidence for a role of dACC E/I balance in patch-leaving decisions.

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