Kainate Receptor-Mediated Modulation of Hippocampal Fast Spiking Interneurons in a Rat Model of Schizophrenia

Kainate receptor (KAR) subunits are believed to be involved in abnormal GABAergic neurotransmission in the hippocampus (HIPP) in schizophrenia (SZ) and bipolar disorder. Postmortem studies have shown changes in the expression of the GluR5/6 subunits of KARs in the stratum oriens (SO) of sectors CA2/3, where the basolateral amygdala (BLA) sends a robust projection. Previous work using a rat model of SZ demonstrated that BLA activation leads to electrophysiological changes in fast-spiking interneurons in SO of CA2/3. The present study explores KAR modulation of interneurons in CA2/3 in response to BLA activation. Intrinsic firing properties of these interneurons through KAR-mediated activity were measured with patch-clamp recordings from rats that received 15 days of picrotoxin infusion into the BLA. Chronic BLA activation induced changes in the firing properties of CA2/3 interneurons associated with modifications in the function of KARs. Specifically, the responsiveness of these interneurons to activation of KARs was diminished in picrotoxin-treated rats, while the after-hyperpolarization (AHP) amplitude was increased. In addition, we tested blockers of KAR subunits which have been shown to have altered gene expression in SO sector CA2/3 of SZ subjects. The GluR5 antagonist UBP296 further decreased AP frequency and increased AHP amplitude in picrotoxin-treated rats. Application of the GluR6/7 antagonist NS102 suggested that activation of GluR6/7 KARs may be required to maintain the high firing rates in SO interneurons in the presence of KA. Moreover, the GluR6/7 KAR-mediated signaling may be suppressed in PICRO-treated rats. Our findings indicate that glutamatergic activity from the BLA may modulate the firing properties of CA2/3 interneurons through GluR5 and GluR6/7 KARs. These receptors are expressed in GABAergic interneurons and play a key role in the synchronization of gamma oscillations. Modulation of interneuronal activity through KARs in response to amygdala activation may lead to abnormal oscillatory rhythms reported in SZ subjects

Research protocol: a synthesis of qualitative studies on the process of adaptation to dependency in elderly persons and their families

Background: Dealing with dependency in the elderly and their families leads us to explore the life experience of those involved together with the processes of adaptation to this condition. A number of original studies have been published which, following a qualitative methodology, have dealt with both dimensions. Methods/Design: Objectives: 1) To present a synthesis of the qualitative evidence available on the process of adaptation to dependency in elderly persons and their families; 2) to conduct an in-depth study into the experiences and strategies developed by both to optimise their living conditions; 3) to enable standards of action/ intervention to be developed in the caregiving environment. A synthesis of qualitative studies is projected with an extensive and inclusive bibliography search strategy. The primary search will focus on the major databases (CINAHL, MEDLINE, EMBASE, PsycInfo, PSICODOC, Cochrane Library, JBI, EMBASE, LILACS, CUIDEN, CUIDEN qualitative, CUIDATGE, British Nursing Index, SSCI). The secondary search will be conducted in articles taken from the references to studies identified in the articles and reports and the manual search in congresses and foundation papers. Article quality will be assessed by the guide proposed by Sandelowski & Barroso and data extraction done using the QARI data extraction form proposed by the Joanna Briggs Institute for Evidence-Based Practice. The synthesis of the findings will be based on the principles and procedures of grounded theory: coding, identification and relationship between categories, and synthesis using constant comparison as a strategy. Discussion: This synthesis of qualitative evidence will enable us to detect health needs as perceived by the receivers in their own interaction contexts.Health Research Spain Fund for financing this Project entitled "A synthesis of qualitative studies on the process of adaptation to dependency in elderly persons and their families", (PI07/90871 Health Ministry) after a peer-reviewed funding process

Homeostatic synaptic scaling: molecular regulators of synaptic AMPA-type glutamate receptors

The ability of neurons and circuits to maintain their excitability and activity levels within the appropriate dynamic range by homeostatic mechanisms is fundamental for brain function. Neuronal hyperactivity, for instance, could cause seizures.  One such homeostatic process is synaptic scaling, also known as synaptic homeostasis. It involves a negative feedback process by which neurons adjust (scale) their postsynaptic strength over their whole synapse population to compensate for increased or decreased overall input thereby preventing neuronal hyper- or hypoactivity that could otherwise result in neuronal network dysfunction. While synaptic scaling is well-established and critical, our understanding of the underlying molecular mechanisms is still in its infancy. Homeostatic adaptation of synaptic strength is achieved through upregulation (upscaling) or downregulation (downscaling) of the functional availability of AMPA-type glutamate receptors (AMPARs) at postsynaptic sites.  Understanding how synaptic AMPARs are modulated in response to alterations in overall neuronal activity is essential to gain valuable insights into how neuronal networks adapt to changes in their environment, as well as the genesis of an array of neurological disorders. Here we discuss the key molecular mechanisms that have been implicated in tuning the synaptic abundance of postsynaptic AMPARs in order to maintain synaptic homeostasis